今日の臨床サポート

乳癌(非浸潤性乳癌)

著者: 宮城由美 がん研有明病院 乳腺外科

監修: 中村清吾 昭和大学医学部外科学講座乳腺外科学部門

著者校正済:2021/10/20
現在監修レビュー中
患者向け説明資料

概要・推奨   

  1. 非浸潤性乳癌は、癌細胞が乳管小葉系にとどまり間質へ浸潤していないものを指す。非浸潤性乳管癌と非浸潤性小葉癌に分類される。
  1. 非浸潤性乳癌はTisN0M0の「0期」である。
  1. 非浸潤性乳癌は全乳癌の約15%、そのほとんどが非浸潤性乳管癌である。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
宮城由美 : 未申告[2021年]
監修:中村清吾 : 講演料(アストラゼネカ,第一三共,中外製薬),研究費・助成金など(CESデカルト,第一三共,シスメックス,アストラゼネカ,島津製作所,大鵬薬品工業),奨学(奨励)寄付など(エーザイ,コニカミノルタ,大鵬薬品工業,中外製薬)[2021年]

改訂のポイント:
  1. 定期レビューを行い、最新の知見に基づいて全体的に見直しを行った。

病態・疫学・診察

病態・疫学  
  1. 非浸潤性乳癌は、癌細胞が乳管小葉系にとどまり間質へ浸潤していないものを指す。非浸潤性乳管癌と非浸潤性小葉癌に分類される[1]
  1. 非浸潤性乳管癌は終末細乳管から発生し、乳管内及び小葉内へ進展する。乳頭型、篩状型、充実型、面疱型など多様な組織像を呈する。嚢胞内癌も非浸潤性乳管癌に含まれる。
  1. 非浸潤性小葉癌は終末乳管小葉系の上皮細胞より発生し、小葉内で充実性に発育し、腺腔形成は示さない。細乳管に進展することもある。
  1. 非浸潤性乳癌は全乳癌の約15%、そのほとんどが非浸潤性乳管癌である[2]。マンモグラフィ検診の普及とともにその割合は増加している。
  1. 多くは非触知で、検診でのマンモグラフィの石灰化像や超音波の非腫瘤性病変として発見されることが多い。
  1. ときに血性乳頭分泌物で発見されることがある。
  1. 手術や放射線といった局所療法のみで根治が期待できる。
  1. 浸潤性乳癌の手術標本上、偶発的に発見されることもある。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
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文献 

著者: Tina W F Yen, Kelly K Hunt, Merrick I Ross, Nadeem Q Mirza, Gildy V Babiera, Funda Meric-Bernstam, S Eva Singletary, W Fraser Symmans, Sharon H Giordano, Barry W Feig, Frederick C Ames, Henry M Kuerer
雑誌名: J Am Coll Surg. 2005 Apr;200(4):516-26. doi: 10.1016/j.jamcollsurg.2004.11.012.
Abstract/Text BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in patients with an initial diagnosis of ductal carcinoma in situ (DCIS) has not been well defined. The purpose of our study was to determine when the risk of finding invasive disease on final pathology in patients with an initial diagnosis of DCIS was sufficiently high to justify use of SLNB.
STUDY DESIGN: The records of 398 consecutive patients from our prospective database with an initial diagnosis of DCIS, treated between July 1999 and December 2002, were analyzed. Associations between clinical and pathologic factors and patient selection for SLNB and outcomes were analyzed for significance using univariate and multivariate analyses.
RESULTS: Of the 398 patients, 80 (20%) were found to have invasive disease on final pathology. Multivariate analysis revealed 4 independent predictors of invasive cancer on final pathology: 55 years of age or younger (odds ratio [OR], 2.19; p = 0.024), diagnosis by core-needle biopsy (OR, 3.76; p = 0.006), mammographic DCIS size of at least 4 cm (OR, 2.92; p = 0.001), and high-grade DCIS (OR, 3.06; p = 0.002). A total of 141 patients (35%) underwent SLNB as a component of their initial operation. Multivariate analysis revealed that the presence of comedonecrosis (OR, 2.69; p = 0.007) and larger mammographic DCIS size (OR, 1.18; p = 0.0002) were independent predictors of patients' undergoing SLNB. Of these 141 patients, 103 (73%) were diagnosed by core-needle biopsy, 42 (30%) had invasive disease on final pathology, and 14 (10%) had a positive sentinel lymph node: 12 (86%) by hematoxylin and eosin staining and 2 by immunohistochemistry. The only independent predictor of a positive SLN was the presence of a palpable tumor (OR, 4.28, p = 0.042). Of these 14 patients with a positive sentinel node, only 11 (79%) had invasive cancer on final pathology.
CONCLUSIONS: SLNB should not be performed routinely for all patients with an initial diagnosis of DCIS. Risks and benefits of SLNB should be discussed with patients who are younger, are diagnosed by core-needle biopsy, or have large or high-grade DCIS.

PMID 15804465  J Am Coll Surg. 2005 Apr;200(4):516-26. doi: 10.1016/j.・・・
著者: Amit Goyal, Anthony Douglas-Jones, Ian Monypenny, Helen Sweetland, Guy Stevens, Robert E Mansel
雑誌名: Breast Cancer Res Treat. 2006 Aug;98(3):311-4. doi: 10.1007/s10549-006-9167-2. Epub 2006 Mar 22.
Abstract/Text BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in patients with a core needle-biopsy diagnosis of ductal carcinoma in situ (DCIS) has been intensely debated. Core needle-biopsy has an inherent sampling error leading to histologic underestimation of invasive disease. If SLNB is not performed at the time of the definitive operative procedure, patients found to have an invasive cancer, will require a second operative procedure. The study was designed to determine when the risk of finding invasive disease on final pathology in patients with an initial diagnosis of DCIS was sufficiently high to justify the use of SLNB.
METHODS: We identified 587 women with an initial core needle-biopsy diagnosis of DCIS in the prospective Breast Test Wales (BTW) database from 1995 through 2005. A variety of clinical, mammographic and histologic features were identified and correlated with the presence of invasion at excision using univariate and multivariate analyses.
RESULTS: Median age of patients at the time of diagnosis was 58 years (range 41 to 83 years). 201 patients (36%) were treated by mastectomy and 354 (64%) by breast conservation surgery. 220 of 587 patients (38%) were found to have invasive disease on final pathology. On univariate analysis, the rate of upstaging was related to the presence of a clinically palpable mass and size of the mass (both p<0.0001, Mann-Whitney test); mammographic presence of a mass and size of the mass (both p<0.0001, Mann-Whitney test). Multivariate logistic regression analysis revealed 2 independent predictors of invasive cancer on final pathology: mass on clinical examination (odds ratio [OR], 5.09; p<0.0001) and mammographic mass (OR, 7.37; p<0.0001). Age, grade of DCIS, microinvasion and presence of comedonecrosis did not help in distinguishing between patients with DCIS and those upstaged to invasive carcinoma at definitive surgery. Axillary nodal staging (four node sampling or clearance) was done at the time of surgery in 269 patients. Axillary nodal metastases were found in 35 of 269 patients (13%). All 35 patients had invasive carcinoma on final pathology.
CONCLUSION: The indiscriminate use of SLNB in patients with DCIS seems excessive. Our study suggests that patients with a mass on clinical examination or mammogram have an increased risk of invasive disease at the time of definitive operative procedure and should undergo SLNB at the initial procedure. In addition, SLNB should be performed in patients undergoing mastectomy because mastectomy precludes SLNB if invasive disease is subsequently discovered.

PMID 16552627  Breast Cancer Res Treat. 2006 Aug;98(3):311-4. doi: 10.・・・
著者: Elizabeth A Mittendorf, Cletus A Arciero, Veronica Gutchell, Jeff Hooke, Craig D Shriver
雑誌名: Curr Surg. 2005 Mar-Apr;62(2):253-7. doi: 10.1016/j.cursur.2004.09.011.
Abstract/Text BACKGROUND: Sentinel lymph node biopsy (SLNB) is a minimally invasive, accurate method of evaluating axillary lymph nodes in patients with invasive cancer. The technique has also been applied successfully in patients with ductal carcinoma in situ (DCIS). The purpose of this study was to review our experience performing SLNB in patients with a biopsy diagnosis of DCIS.
METHODS: A prospective study of consecutive patients seen at our institution from August 2001 to April 2004 with a biopsy diagnosis of DCIS was undertaken. Demographic data, biopsy method, final pathology, and surgical treatment were recorded. Patients undergoing SLNB were identified, and pathologic results were noted.
RESULTS: Eighty-five patients with a biopsy diagnosis of DCIS were treated. Fifty-five (64.7%) had their diagnosis made by excisional biopsy, and 30 (35.3%) by core biopsy. Forty-four (51.7%) patients underwent SLNB as part of their definitive surgical procedure, and an SLN was successfully identified in 41 (93.2%). Nine (22.0%) patients who underwent successful SLNB had a positive SLN, 2 by hematoxylin and eosin (H&E) staining and 7 by immunohistochemical (IHC) staining for cytokeratin. Both patients with H&E-positive SLN were ultimately found to have invasive disease in their primary lesion. Final pathologic assessment of all primary lesions revealed invasive carcinoma in 7, 6 of whom had their diagnosis made by core biopsy. Overall, 20.0% of patients with a core biopsy diagnosis of DCIS were upstaged to invasive disease. Whether the lesion was palpable, grade and the presence or absence of necrosis were not significantly different in patients ultimately found to have invasive disease versus those who did not.
DISCUSSION: Sentinel lymph node biopsy can be performed accurately in patients with a biopsy diagnosis of DCIS. The rate of axillary disease in patients with pure, completely resected DCIS is low; therefore, SLNB is not indicated in all patients with this biopsy diagnosis. Because of a high rate of invasive disease on the final pathology of patients with DCIS diagnosed by core biopsy, these patients should be offered SLNB.

PMID 15796952  Curr Surg. 2005 Mar-Apr;62(2):253-7. doi: 10.1016/j.cur・・・
著者: C Boetes, R D Mus, R Holland, J O Barentsz, S P Strijk, T Wobbes, J H Hendriks, S H Ruys
雑誌名: Radiology. 1995 Dec;197(3):743-7. doi: 10.1148/radiology.197.3.7480749.
Abstract/Text PURPOSE: To evaluate the comparative accuracy of magnetic resonance (MR) imaging relative to mammography and ultrasonography (US) for assessing the extent of breast tumors.
MATERIALS AND METHODS: Histologic results and preoperative imaging findings (mammography, US, MR imaging) were analyzed regarding tumor size and multifocality of 61 tumors in 60 women undergoing mastectomy for carcinoma.
RESULTS: In 10% of cases, the index tumor was not seen at mammography. With US, 15% of the index tumors were not recognized, while MR imaging missed 2% of the index tumors. On mammographic and US images, tumor size was underestimated significantly (P < .005), by 14% and 18%, respectively, while MR imaging showed no significant difference in size compared with that found in a pathologic evaluation. Mammography showed 31% of the additional invasive lesions, while US showed 38% and MR imaging showed 100%.
CONCLUSION: MR imaging was the most accurate of the three preoperative imaging modalities in assessing the size and number of malignant lesions in the breast.

PMID 7480749  Radiology. 1995 Dec;197(3):743-7. doi: 10.1148/radiolog・・・
著者: Jacopo Nori, Icro Meattini, Elisabetta Giannotti, Dalmar Abdulcadir, Giovanna Mariscotti, Massimo Calabrese, Francesca Angelino, Fabio Chiesa, Calogero Saieva, Ermanno Vanzi, Cecilia Boeri, Simonetta Bianchi, Luis Sanchez, Lorenzo Orzalesi, Donato Casella, Tommaso Susini, Lorenzo Livi
雑誌名: Breast J. 2014 May-Jun;20(3):243-8. doi: 10.1111/tbj.12250.
Abstract/Text Ductal carcinoma in situ (DCIS) is a common neoplasm that may be associated with focal invasive breast cancer lesions. The aim of our study was to evaluate the role of preoperative magnetic resonance imaging (MRI) in determining occult invasive presence and disease extent in patients with preoperative diagnosis of pure DCIS. We analyzed 125 patients with postoperative pure DCIS (n = 91) and DCIS plus invasive component (n = 34). Diagnostic mammography (MRX) showed a size underestimation rate of 30.4% while MRI showed an overestimation rate of 28.6%. Comparing the mean absolute error between preoperative MRI and MRX evaluations and final disease extent, MRI showed an improved accuracy of 51.2%. In our analysis preoperative breast MRI showed a better accuracy in predicting postoperative pathologic extent of disease, adding strength to the growing evidences that preoperative MRI can lead to a more appropriate management of DCIS patients.

© 2014 Wiley Periodicals, Inc.
PMID 24750509  Breast J. 2014 May-Jun;20(3):243-8. doi: 10.1111/tbj.12・・・
著者: M E Brennan, N Houssami
雑誌名: Breast. 2012 Apr;21(2):112-23. doi: 10.1016/j.breast.2011.10.005. Epub 2011 Nov 16.
Abstract/Text While guidelines recommend against routine use of staging imaging to detect asymptomatic distant metastases (DM) in newly diagnosed breast cancer (BC), modern imaging technologies may have improved detection capability and may have a role in some cases. We performed a systematic review of studies (1995-2011) evaluating the prevalence of DM and the accuracy of staging imaging for detection of asymptomatic DM. Twenty-two studies reporting on 14,824 BC subjects (median age 53 years) undergoing staging imaging were eligible. Median prevalence of DM was 7.0% (range 1.2-48.8%); prevalence increased with increasing BC stage. Conventional imaging studies had lower DM prevalence than studies of PET(PET/CT). Imaging median sensitivity/specificity respectively were: combined conventional imaging 78.0%/91.4%; bone scintigraphy 98.0%/93.5%; chest X-ray 100%/97.9%; liver ultrasound 100%/96.7%; CT chest/abdomen 100%/93.1%; FDG-PET 100.0%/96.5%; FDG-PET/CT 100%/98.1%. Low prevalence of DM was seen in Stage I-II BC with much higher prevalence in more advanced disease. Accuracy of PET modalities was very high however the high proportion of detected asymptomatic DM partly reflects selection bias.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 22094116  Breast. 2012 Apr;21(2):112-23. doi: 10.1016/j.breast.20・・・
著者: Simona F Shaitelman, J Ben Wilkinson, Larry L Kestin, Hong Ye, Neal S Goldstein, Alvaro A Martinez, Frank A Vicini
雑誌名: Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):e305-12. doi: 10.1016/j.ijrobp.2011.12.092. Epub 2012 Mar 13.
Abstract/Text PURPOSE: To determine 20-year rates of local control and outcome-associated factors for ductal carcinoma in situ (DCIS) after breast-conserving therapy (BCT).
METHODS AND MATERIALS: All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival.
RESULTS: One hundred forty-five cases were evaluated; the median follow-up time was 19.3 years. IBTR developed in 25 patients, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. One third of IBTRs were elsewhere failures, and 68% of IBTRs occurred <10 years after diagnosis. Young age and cancerization of lobules predicted for IBTR at <10 years, and increased slide involvement and atypical ductal hyperplasia were associated with IBTR at later time points.
CONCLUSIONS: Patients with DCIS treated with BCT have excellent long-term rates of local control. Predictors of IBTR vary over time, and the risk of recurrence seems highest within 10 to 12 years after diagnosis.

Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 22417804  Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):e305-12.・・・
著者: Cristiana Vidali, Orazio Caffo, Cynthia Aristei, Filippo Bertoni, Alberto Bonetta, Marina Guenzi, Cinzia Iotti, Maria Cristina Leonardi, Salvatore Mussari, Stefano Neri, Nicoletta Pietta
雑誌名: Radiat Oncol. 2012 Oct 25;7:177. doi: 10.1186/1748-717X-7-177. Epub 2012 Oct 25.
Abstract/Text BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased markedly in recent decades. In the past, mastectomy was the primary treatment for patients with DCIS, but as with invasive cancer, breast-conserving surgery followed by radiation therapy (RT) has become the standard approach. We present the final results of a multi-institutional retrospective study of an Italian Radiation Oncology Group for the study of conservative treatment of DCIS, characterized by a very long period of accrual, from February 1985 to March 2000, and a median follow-up longer than 11 years.
METHODS: A collaborative multi-institutional study was conducted in Italy in 10 Radiation Oncology Departments. A consecutive series of 586 women with DCIS histologically confirmed, treated between February 1985 and March 2000, was retrospectively evaluated. Median age at diagnosis was 55 years (range: 29-84); 32 patients were 40 years old or younger. All women underwent conservative surgery followed by whole breast RT. Irradiation was delivered to the entire breast, for a median total dose of 50 Gy; the tumour bed was boosted in 295 cases (50%) at a median dose of 10 Gy.
RESULTS: After a median follow-up of 136 months (range: 16-292 months), 59/586 patients (10%) experienced a local recurrence: invasive in 37 cases, intraductal in 20 and not specified in two. Salvage mastectomy was the treatment of choice in 46 recurrent patients; conservative surgery in 10 and it was unknown in three patients. The incidence of local recurrence was significantly higher in women younger than 40 years (31.3%) (p= 0.0009). Five patients developed distant metastases. Furthermore 40 patients developed a contralateral breast cancer and 31 a second primary tumour in a different site. The 10-year actuarial overall survival (OS) was 95.5% and the 10-year actuarial disease-specific survival (DSS) was 99%.
CONCLUSIONS: Our results are consistent with those reported in the literature. In particular it has been defined the importance of young age (40 years or less) as a relevant risk factor for local recurrence. This retrospective multi-institutional Italian study confirms the long term efficacy of breast conserving surgery with RT in women with DCIS.

PMID 23098066  Radiat Oncol. 2012 Oct 25;7:177. doi: 10.1186/1748-717X・・・
著者: L M van Roozendaal, B Goorts, M Klinkert, K B M I Keymeulen, B De Vries, L J A Strobbe, C A P Wauters, Y E van Riet, E Degreef, E J T Rutgers, J Wesseling, M L Smidt
雑誌名: Breast Cancer Res Treat. 2016 Apr;156(3):517-525. doi: 10.1007/s10549-016-3783-2. Epub 2016 Apr 15.
Abstract/Text Breast cancer guidelines advise sentinel lymph node biopsy (SLNB) in patients with ductal carcinoma in situ (DCIS) on core biopsy at high risk of invasive cancer or in case of mastectomy. This study investigates the incidence of SLNB and SLN metastases and the relevance of indications in guidelines and literature to perform SLNB in order to validate whether SLNB is justified in patients with DCIS on core biopsy in current era. Clinically node negative patients diagnosed from 2004 to 2013 with only DCIS on core needle biopsy were selected from a national database. Incidence of SLN biopsy and metastases was calculated. With Fisher exact tests correlation between SLNB indications and actual presence of SLN metastases was studied. Further, underestimation rate for invasive cancer and correlation with SLN metastases was analysed. 910 patients were included. SLNB was performed in 471 patients (51.8 %): 94.5 % had pN0, 3.0 % pN1mi and 2.5 % pN1. Patients undergoing mastectomy had 7 % SLN metastases versus 3.5 % for breast conserving surgery (BCS) (p = 0.107). The only factors correlating to SLN metastases were smaller core needle size (p = 0.01) and invasive cancer (p < 0.001). Invasive cancer was detected in 16.7 % by histopathology with 15.6 % SLN metastases versus only 2 % in pure DCIS. SLNB showed metastases in 5.5 % of patients; 3.5 % in case of BCS (any histopathology) and 2 % when pure DCIS was found at definitive histopathology (BCS and mastectomy). Consequently, SLNB should no longer be performed in patients diagnosed with DCIS on core biopsy undergoing BCS. If definitive histopathology shows invasive cancer, SLNB can still be considered after initial surgery.

PMID 27083179  Breast Cancer Res Treat. 2016 Apr;156(3):517-525. doi: ・・・
著者: Keiichiro Tada, Akiko Ogiya, Kiyomi Kimura, Hidetomo Morizono, Kotaro Iijima, Yumi Miyagi, Seiichiro Nishimura, Masujiro Makita, Rie Horii, Futoshi Akiyama, Takuji Iwase
雑誌名: World J Surg Oncol. 2010 Jan 27;8:6. doi: 10.1186/1477-7819-8-6. Epub 2010 Jan 27.
Abstract/Text BACKGROUND: The impact of sentinel lymph node biopsy on breast cancer mimicking ductal carcinoma in situ (DCIS) is a matter of debate.
METHODS: We studied the rate of occurrence of sentinel lymph node metastasis in 255 breast cancer patients with pure DCIS showing no invasive components on routine pathological examination. We compared this to the rate of occurrence in 177 patients with predominant intraductal-component (IDC) breast cancers containing invasive foci equal to or less than 0.5 cm in size.
RESULTS: Most of the clinical and pathological baseline characteristics were the same between the two groups. However, peritumoral lymphatic permeation occurred less often in the pure DCIS group than in the IDC-predominant invasive-lesion group (1.2% vs. 6.8%, p = 0.002). One patient (0.39%) with pure DCIS had two sentinel lymph nodes positive for metastasis. This rate was significantly lower than that in patients with IDC-predominant invasive lesions (6.2%; p < 0.001).
CONCLUSIONS: Because the rate of sentinel lymph node metastasis in pure DCIS is very low, sentinel lymph node biopsy can safely be omitted.

PMID 20105298  World J Surg Oncol. 2010 Jan 27;8:6. doi: 10.1186/1477-・・・
著者: Sibel Ozkan-Gurdal, Neslihan Cabioglu, Beyza Ozcinar, Mahmut Muslumanoglu, Vahit Ozmen, Mustafa Kecer, Ekrem Yavuz, Abdullah Igci
雑誌名: Asian Pac J Cancer Prev. 2014;15(1):55-60. doi: 10.7314/apjcp.2014.15.1.55.
Abstract/Text BACKGROUND: Whether sentinel lymph node biopsy (SLNB) should be performed in patients with pure ductal carcinoma in situ (DCIS) of the breast has been a question of debate over the last decade. The aim of this study was to identify factors associated with microinvasive disease and determine the criteria for performing SLNB in patients with DCIS.
MATERIALS AND METHODS: 125 patients with DCIS who underwent surgery between January 2000 and December 2008 were reviewed to identify factors associated with DCIS and DCIS with microinvasion (DCISM).
RESULTS: 88 patients (70.4%) had pure DCIS and 37 (29.6%) had DCISM. Among 33 DCIS patients who underwent SLNB, one patient (3.3%) was found to have isolated tumor cells in her biopsy, whereas 1 of 14 (37.8%) patients with DCISM had micrometastasis (7.1%). Similarly, of 16 patients (18.2%) with pure DCIS and axillary lymph node dissection (ALND) without SLNB, none had lymph node metastasis. Furthermore, of 20 patients with DCISM and ALND, only one (5%) had metastasis. In multivariate analysis, the presence of comedo necrosis [relative risk (RR)=4.1, 95% confidence interval (CI)=1.6-10.6, P=0.004], and hormone receptor (ER or PR) negativity (RR=4.0, 95%CI=1.5-11, P=0.007), were found to be significantly associated with microinvasion.
CONCLUSIONS: Our findings suggest patients presenting with a preoperative diagnosis of DCIS associated with comedo necrosis or hormone receptor negativity are more likely to have a microinvasive component in definitive pathology following surgery, and should be considered for SLNB procedure along with patients who will undergo mastectomy due to DCIS.

PMID 24528005  Asian Pac J Cancer Prev. 2014;15(1):55-60. doi: 10.7314・・・
著者: Marjorie M Luckey, Nigel Gilchrist, Henry G Bone, Michael W Davie, Tobias J de Villiers, Mei Wu, Anastasia G Daifotis, Arthur C Santora, John J Orloff
雑誌名: Obstet Gynecol. 2003 Apr;101(4):711-21.
Abstract/Text OBJECTIVE: To evaluate the efficacy and safety of alendronate 35 mg once weekly compared with alendronate 5 mg daily in the prevention of osteoporosis.
METHODS: We compared the efficacy and safety of treatment with alendronate 35 mg once weekly (n = 362) and alendronate 5 mg daily (n = 361) in a 1-year, double-blind, multicenter study of postmenopausal women (6 months or greater), aged 40-70 years, with lumbar spine and femoral neck bone mineral density T-scores between -2.5 and 1. The primary efficacy end point was the comparability of lumbar spine bone mineral density increases, defined by strict prespecified criteria.
RESULTS: Mean increases in lumbar spine bone mineral density at 12 months were equivalent (difference between the alendronate 35-mg once-weekly group and the alendronate 5-mg daily group [90% confidence interval] at month 12 was -0.3% [-0.6, 0.1], well within the prespecified bounds of +/-1.0%). Bone mineral density increases at other skeletal sites and effects on bone turnover were also virtually identical for the two dosing regimens. Both treatment regimens were well tolerated, and the larger weekly unit dose was not associated with an increased frequency of upper gastrointestinal events.
CONCLUSION: Alendronate 35 mg once weekly is therapeutically equivalent to alendronate 5 mg daily and provides patients with greater dosing convenience, in addition to the proven efficacy of alendronate and good tolerability.

PMID 12681875  Obstet Gynecol. 2003 Apr;101(4):711-21.
著者: Lotte E Elshof, Konstantinos Tryfonidis, Leen Slaets, A Elise van Leeuwen-Stok, Victoria P Skinner, Nicolas Dif, Ruud M Pijnappel, Nina Bijker, Emiel J Th Rutgers, Jelle Wesseling
雑誌名: Eur J Cancer. 2015 Aug;51(12):1497-510. doi: 10.1016/j.ejca.2015.05.008. Epub 2015 May 26.
Abstract/Text BACKGROUND: The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non- to slow-growing low-grade DCIS. The LORD study aims to evaluate the safety of active surveillance in women with low-risk DCIS.
DESIGN: This is a randomised, international multicentre, open-label, phase III non-inferiority trial, led by the Dutch Breast Cancer Research Group (BOOG 2014-04) and the European Organization for Research and Treatment of Cancer (EORTC-BCG 1401). Standard treatment will be compared to active surveillance in 1240 women aged ⩾ 45 years with asymptomatic, screen-detected, pure low-grade DCIS based on vacuum-assisted biopsies of microcalcifications only. Both study arms will be monitored with annual digital mammography for a period of 10 years. The primary end-point is 10-year ipsilateral invasive breast cancer free percentage. Secondary end-points include patient reported outcomes, diagnostic biopsy rate during follow-up, ipsilateral mastectomy rate and translational research.
FEASIBILITY: To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres.

Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
PMID 26025767  Eur J Cancer. 2015 Aug;51(12):1497-510. doi: 10.1016/j.・・・
著者: Adele Francis, Jeremy Thomas, Lesley Fallowfield, Matthew Wallis, John M S Bartlett, Cassandra Brookes, Tracy Roberts, Sarah Pirrie, Claire Gaunt, Jennie Young, Lucinda Billingham, David Dodwell, Andrew Hanby, Sarah E Pinder, Andrew Evans, Malcolm Reed, Valerie Jenkins, Lucy Matthews, Maggie Wilcox, Patricia Fairbrother, Sarah Bowden, Daniel Rea
雑誌名: Eur J Cancer. 2015 Nov;51(16):2296-303. doi: 10.1016/j.ejca.2015.07.017. Epub 2015 Aug 18.
Abstract/Text Overdiagnosis, and thus overtreatment, are inevitable consequences of most screening programmes; identification of ways of minimising the impact of overdiagnosis demands new prospective research, in particular the need to separate clinically relevant lesions that require active treatment from those that can be safely left alone or monitored and only need treated if they change characteristics. Breast cancer screening has led to a large increase in ductal carcinoma in situ (DCIS) diagnoses. This is a widely heterogeneous disease and most DCIS detected through screening is of high cytonuclear grade and therefore likely to be important clinically. However, the historic practice of surgical treatment for all DCIS is unlikely to be optimal for lower risk patients. A clearer understanding of how to manage DCIS is required. This article describes the background and development of 'The low risk' DCIS trial (LORIS), a phase III trial of surgery versus active monitoring. LORIS will determine if it is appropriate to manage women with screen detected or asymptomatic, low grade and intermediate grade DCIS with low grade features, by active monitoring rather than by surgical treatment.

Copyright © 2015 Elsevier Ltd. All rights reserved.
PMID 26296293  Eur J Cancer. 2015 Nov;51(16):2296-303. doi: 10.1016/j.・・・
著者: Jocelyn Lippey, Andrew Spillane, Christobel Saunders
雑誌名: ANZ J Surg. 2016 Nov;86(11):859-860. doi: 10.1111/ans.13659.
Abstract/Text
PMID 27784140  ANZ J Surg. 2016 Nov;86(11):859-860. doi: 10.1111/ans.1・・・
著者: E Shelley Hwang, Terry Hyslop, Thomas Lynch, Elizabeth Frank, Donna Pinto, Desiree Basila, Deborah Collyar, Antonia Bennett, Celia Kaplan, Shoshana Rosenberg, Alastair Thompson, Anna Weiss, Ann Partridge
雑誌名: BMJ Open. 2019 Mar 12;9(3):e026797. doi: 10.1136/bmjopen-2018-026797. Epub 2019 Mar 12.
Abstract/Text INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-invasive non-obligate precursor of invasive breast cancer. With guideline concordant care (GCC), DCIS outcomes are at least as favourable as some other early stage cancer types such as prostate cancer, for which active surveillance (AS) is a standard of care option. However, AS has not yet been tested in relation to DCIS. The goal of the COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial for low-risk DCIS is to gather evidence to help future patients consider the range of treatment choices for low-risk DCIS, from standard therapies to AS. The trial will determine whether there may be some women who do not substantially benefit from current GCC and who could thus be safely managed with AS. This protocol is version 5 (11 July 2018). Any future protocol amendments will be submitted to Quorum Centralised Institutional Review Board/local institutional review boards for approval via the sponsor of the study (Alliance Foundation Trials).
METHODS AND ANALYSIS: COMET is a phase III, randomised controlled clinical trial for patients with low-risk DCIS. The primary outcome is ipsilateral invasive breast cancer rate in women undergoing GCC compared with AS. Secondary objectives will be to compare surgical, oncological and patient-reported outcomes. Patients randomised to the GCC group will undergo surgery as well as radiotherapy when appropriate; those in the AS group will be monitored closely with surgery only on identification of invasive breast cancer. Patients in both the GCC and AS groups will have the option of endocrine therapy. The total planned accrual goal is 1200 patients.
ETHICS AND DISSEMINATION: The COMET trial will be subject to biannual formal review at the Alliance Foundation Data Safety Monitoring Board meetings. Interim analyses for futility/safety will be completed annually, with reporting following Consolidated Standards of Reporting Trials (CONSORT) guidelines for non-inferiority trials.
TRIAL REGISTRATION NUMBER: NCT02926911; Pre-results.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PMID 30862637  BMJ Open. 2019 Mar 12;9(3):e026797. doi: 10.1136/bmjope・・・
著者: Annabel Goodwin, Sharon Parker, Davina Ghersi, Nicholas Wilcken
雑誌名: Cochrane Database Syst Rev. 2009 Jul 8;(3):CD000563. doi: 10.1002/14651858.CD000563.pub5. Epub 2009 Jul 8.
Abstract/Text BACKGROUND: The addition of radiotherapy (RT) following breast conserving surgery (BCS) was first shown to reduce the risk of ipsilateral recurrence in the treatment of invasive breast cancer. Ductal carcinoma in situ (DCIS) is a pre-invasive lesion. Recurrence of ipsilateral disease following BCS can be either DCIS or invasive breast cancer. Randomised controlled trials (RCTs) have shown that RT can reduce the risk of recurrence, but assessment of potential long-term complications from addition of RT following BSC for DCIS has not been reported for women participating in RCTs.
OBJECTIVES: To summarise the data from RCTs testing the addition of RT to BCS for treatment of DCIS to determine the balance between the benefits and harms.
SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Specialised Register (January 2008), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 1), MEDLINE (February 2008), and EMBASE (February 2008). Reference lists of articles and handsearching of ASCO (2007), ESMO (2002 to 2007), and St Gallen (2005 to 2007) conferences were performed.
SELECTION CRITERIA: RCTs of breast conserving surgery with and without radiotherapy in women at first diagnosis of pure ductal carcinoma in situ (no invasive disease present).
DATA COLLECTION AND ANALYSIS: Two authors independently assessed each potentially eligible trial for inclusion and its quality. Two authors also independently extracted data from published Kaplan-Meier analysis (survival curves) and reported summary statistics. Data were extracted and pooled for four trials. Data for planned subgroups were extracted and pooled for analysis.There were insufficient data to pool for long-term toxicity from radiotherapy.
MAIN RESULTS: Four RCTs involving 3925 women were identified and included in this review. All were high quality with minimal risk of bias. Three trials compared the addition of RT to BCS. One trial was a two by two factorial design comparing the use of RT and tamoxifen, each separately or together, in which participants were randomised in at least one arm. Analysis confirmed a statistically significant benefit from the addition of radiotherapy on all ipsilateral breast events (hazards ratio (HR) 0.49; 95% CI 0.41 to 0.59, P < 0.00001) and ipsilateral DCIS recurrence (HR 0.64; 95% CI 0.41 to 1.01, P = 0.05). Pooled analysis for invasive recurrence did not reach statistical significance. All the subgroups analysed benefited from addition of radiotherapy. No significant long-term toxicity from radiotherapy was found. No information about short-term toxicity from radiotherapy or quality of life data were reported.
AUTHORS' CONCLUSIONS: This review confirms the benefit of adding radiotherapy to breast conserving surgery for the treatment of all women diagnosed with DCIS. No long-term toxicity from use of radiotherapy was identified.

PMID 19588320  Cochrane Database Syst Rev. 2009 Jul 8;(3):CD000563. do・・・
著者: Julia S Wong, Carolyn M Kaelin, Susan L Troyan, Michele A Gadd, Rebecca Gelman, Susan C Lester, Stuart J Schnitt, Dennis C Sgroi, Barbara J Silver, Jay R Harris, Barbara L Smith
雑誌名: J Clin Oncol. 2006 Mar 1;24(7):1031-6. doi: 10.1200/JCO.2005.02.9975. Epub 2006 Feb 6.
Abstract/Text PURPOSE: It has been hypothesized that wide excision alone with margins > or = 1 cm may be adequate treatment for small, grade 1 or 2 ductal carcinoma in situ (DCIS). To test this hypothesis, we conducted a prospective, single-arm trial.
METHODS: Entry criteria included DCIS of predominant grade 1 or 2 with a mammographic extent of < or = 2.5 cm treated with wide excision with final margins of > or = 1 cm or a re-excision without residual DCIS. Tamoxifen was not permitted. The accrual goal was 200 patients.
RESULTS: In July 2002, the study closed to accrual at 158 patients because the number of local recurrences met the predetermined stopping rules. The median age was 51 and the median follow-up time was 40 months. Thirteen patients developed local recurrence as the first site of treatment failure 7 to 63 months after study entry. The rate of ipsilateral local recurrence as first site of treatment failure was 2.4% per patient-year, corresponding to a 5-year rate of 12%. Nine patients (69%) experienced recurrence of DCIS and four (31%) experienced recurrence with invasive disease. Twelve recurrences were detected mammographically and one was palpable. Ten were in the same quadrant as the initial DCIS and three were elsewhere within the ipsilateral breast. No patient had positive axillary nodes at recurrence or subsequent metastatic disease.
CONCLUSION: Despite margins of > or = 1 cm, the local recurrence rate is substantial when patients with small, grade 1 or 2 DCIS are treated with wide excision alone. This risk should be considered in assessing the possible use of radiation therapy with or without tamoxifen in these patients.

PMID 16461781  J Clin Oncol. 2006 Mar 1;24(7):1031-6. doi: 10.1200/JCO・・・
著者: Lorie L Hughes, Molin Wang, David L Page, Robert Gray, Lawrence J Solin, Nancy E Davidson, Mary Ann Lowen, James N Ingle, Abram Recht, William C Wood
雑誌名: J Clin Oncol. 2009 Nov 10;27(32):5319-24. doi: 10.1200/JCO.2009.21.8560. Epub 2009 Oct 13.
Abstract/Text PURPOSE: To determine the risk of ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) treated with local excision without irradiation.
PATIENTS AND METHODS: Patients with either low- or intermediate-grade DCIS measuring 2.5 cm or smaller, or high-grade DCIS measuring 1 cm or smaller who had microscopic margin widths of 3 mm or wider and no residual calcifications on postoperative mammograms were eligible for a prospective trial conducted from 1997 to 2002 by the Eastern Cooperative Oncology Group and North Central Cancer Treatment Group. Patients entered in 2000 and later could take tamoxifen if they wished. Median age at last surgery for the entire population was 60 years (range, 28 to 88 years), and median tumor sizes in the two strata were 6 mm and 5 mm, respectively.
RESULTS: With a median follow-up of 6.2 years, the 5-year rate of ipsilateral breast events in the 565 eligible patients in the low/intermediate grade stratum was 6.1% (95% CI, 4.1% to 8.2%). With a median follow-up of 6.7 years, this incidence for the 105 eligible patients in the high-grade stratum was 15.3% (95% CI, 8.2% to 22.5%).
CONCLUSION: Rigorously evaluated and selected patients with low- to intermediate-grade DCIS with margins 3 mm or wider had an acceptably low rate of ipsilateral breast events at 5 years after excision without irradiation. Patients with high-grade lesions had a much higher rate, suggesting that excision alone is inadequate treatment. Further follow-up is necessary to document long-term results.

PMID 19826126  J Clin Oncol. 2009 Nov 10;27(32):5319-24. doi: 10.1200/・・・
著者: Jack Cuzick, Ivana Sestak, Sarah E Pinder, Ian O Ellis, Sharon Forsyth, Nigel J Bundred, John F Forbes, Hugh Bishop, Ian S Fentiman, William D George
雑誌名: Lancet Oncol. 2011 Jan;12(1):21-9. doi: 10.1016/S1470-2045(10)70266-7. Epub 2010 Dec 7.
Abstract/Text BACKGROUND: Initial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial.
METHODS: Women with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870.
FINDINGS: Between May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9-14·7), 376 (163 invasive [122 ipsilateral vs 39 contralateral], 197 DCIS [174 ipsilateral vs 17 contralateral], and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio [HR] 0·41, 95% CI 0·30-0·56; p<0·0001), reducing the incidence of ipsilateral invasive disease (0·32, 0·19-0·56; p<0·0001) as well as ipsilateral DCIS (0·38, 0·22-0·63; p<0·0001), but having no effect on contralateral breast cancer (0·84, 0·45-1·58; p=0·6). Tamoxifen reduced the incidence of all new breast events (HR 0·71, 95% CI 0·58-0·88; p=0·002), reducing recurrent ipsilateral DCIS (0·70, 0·51-0·86; p=0·03) and contralateral tumours (0·44, 0·25-0·77; p=0·005), but having no effect on ipsilateral invasive disease (0·95, 0·66-1·38; p=0·8). No data on adverse events except cause of death were collected for this trial.
INTERPRETATION: This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision.
FUNDING: Cancer Research UK and the Australian National Health and Medical Research Council.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 21145284  Lancet Oncol. 2011 Jan;12(1):21-9. doi: 10.1016/S1470-2・・・
著者: D Craig Allred, Stewart J Anderson, Soonmyung Paik, D Lawrence Wickerham, Iris D Nagtegaal, Sandra M Swain, Elefetherios P Mamounas, Thomas B Julian, Charles E Geyer, Joseph P Costantino, Stephanie R Land, Norman Wolmark
雑誌名: J Clin Oncol. 2012 Apr 20;30(12):1268-73. doi: 10.1200/JCO.2010.34.0141. Epub 2012 Mar 5.
Abstract/Text PURPOSE: The NSABP (National Surgical Adjuvant Breast and Bowel Project) B-24 study demonstrated significant benefit with adjuvant tamoxifen in patients with ductal carcinoma in situ (DCIS) after lumpectomy and radiation. Patients were enrolled without knowledge of hormone receptor status. The current study retrospectively evaluated the relationship between receptors and response to tamoxifen.
PATIENTS AND METHODS: Estrogen (ER) and progesterone receptors (PgR) were evaluated in 732 patients with DCIS (41% of original study population). An experienced central laboratory determined receptor status in all patient cases with available paraffin blocks (n = 449) by immunohistochemistry (IHC) using comprehensively validated assays. Results for additional patients (n = 283) determined by various methods (primarily IHC) were available from enrolling institutions. Combined results were evaluated for benefit of tamoxifen by receptor status at 10 years and overall follow-up (median, 14.5 years).
RESULTS: ER was positive in 76% of patients. Patients with ER-positive DCIS treated with tamoxifen (v placebo) showed significant decreases in subsequent breast cancer at 10 years (hazard ratio [HR], 0.49; P < .001) and overall follow-up (HR, 0.60; P = .003), which remained significant in multivariable analysis (overall HR, 0.64; P = .003). Results were similar, but less significant, when subsequent ipsilateral and contralateral, invasive and noninvasive, breast cancers were considered separately. No significant benefit was observed in ER-negative DCIS. PgR and either receptor were positive in 66% and 79% of patients, respectively, and in general, neither was more predictive than ER alone.
CONCLUSION: Patients in NSABP B-24 with ER-positive DCIS receiving adjuvant tamoxifen after standard therapy showed significant reductions in subsequent breast cancer. The use of adjuvant tamoxifen should be considered for patients with DCIS.

PMID 22393101  J Clin Oncol. 2012 Apr 20;30(12):1268-73. doi: 10.1200/・・・
著者: John F Forbes, Ivana Sestak, Anthony Howell, Bernardo Bonanni, Nigel Bundred, Christelle Levy, Gunter von Minckwitz, Wolfgang Eiermann, Patrick Neven, Michael Stierer, Chris Holcombe, Robert E Coleman, Louise Jones, Ian Ellis, Jack Cuzick, IBIS-II investigators
雑誌名: Lancet. 2016 Feb 27;387(10021):866-73. doi: 10.1016/S0140-6736(15)01129-0. Epub 2015 Dec 11.
Abstract/Text BACKGROUND: Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS.
METHODS: In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358.
RESULTS: Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6-8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64-1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58-1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen.
CONCLUSIONS: No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences.
FUNDING: Cancer Research UK, National Health and Medical Research Council Australia, Breast Cancer Research Fund, AstraZeneca, Sanofi Aventis.

Copyright © 2016 Forbes et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
PMID 26686313  Lancet. 2016 Feb 27;387(10021):866-73. doi: 10.1016/S01・・・
著者: Richard G Margolese, Reena S Cecchini, Thomas B Julian, Patricia A Ganz, Joseph P Costantino, Laura A Vallow, Kathy S Albain, Patrick W Whitworth, Mary E Cianfrocca, Adam M Brufsky, Howard M Gross, Gamini S Soori, Judith O Hopkins, Louis Fehrenbacher, Keren Sturtz, Timothy F Wozniak, Thomas E Seay, Eleftherios P Mamounas, Norman Wolmark
雑誌名: Lancet. 2016 Feb 27;387(10021):849-56. doi: 10.1016/S0140-6736(15)01168-X. Epub 2015 Dec 11.
Abstract/Text BACKGROUND: Ductal carcinoma in situ is currently managed with excision, radiotherapy, and adjuvant hormone therapy, usually tamoxifen. We postulated that an aromatase inhibitor would be safer and more effective. We therefore undertook this trial to compare anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy.
METHODS: The double-blind, randomised, phase 3 National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 trial was done in 333 participating NSABP centres in the USA and Canada. Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole-breast irradiation were enrolled and randomly assigned (1:1) to receive either oral tamoxifen 20 mg per day (with matching placebo in place of anastrozole) or oral anastrozole 1 mg per day (with matching placebo in place of tamoxifen) for 5 years. Randomisation was stratified by age (<60 vs ≥60 years) and patients and investigators were masked to treatment allocation. The primary outcome was breast cancer-free interval, defined as time from randomisation to any breast cancer event (local, regional, or distant recurrence, or contralateral breast cancer, invasive disease, or ductal carcinoma in situ), analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00053898, and is complete.
FINDINGS: Between Jan 1, 2003, and June 15, 2006, 3104 eligible patients were enrolled and randomly assigned to the two treatment groups (1552 to tamoxifen and 1552 to anastrozole). As of Feb 28, 2015, follow-up information was available for 3083 patients for overall survival and 3077 for all other disease-free endpoints, with median follow-up of 9·0 years (IQR 8·2-10·0). In total, 212 breast cancer-free interval events occurred: 122 in the tamoxifen group and 90 in the anastrozole group (HR 0·73 [95% CI 0·56-0·96], p=0·0234). A significant time-by-treatment interaction (p=0·0410) became evident later in the study. There was also a significant interaction between treatment and age group (p=0·0379), showing that anastrozole is superior only in women younger than 60 years of age. Adverse events did not differ between the groups, except for thrombosis or embolism--a known side-effect of tamoxifen-for which there were 17 grade 4 or worse events in the tamoxifen group versus four in the anastrozole group.
INTERPRETATION: Compared with tamoxifen, anastrozole treatment provided a significant improvement in breast cancer-free interval, mainly in women younger than 60 years of age. This finding means that women will benefit from having a choice of effective agents for ductal carcinoma in situ.
FUNDING: US National Cancer Institute and AstraZeneca Pharmaceuticals LP.

Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID 26686957  Lancet. 2016 Feb 27;387(10021):849-56. doi: 10.1016/S01・・・
著者: L F Paszat, R Sutradhar, S Gu, E Rakovitch
雑誌名: Curr Oncol. 2016 Dec;23(6):e538-e545. doi: 10.3747/co.23.3399. Epub 2016 Dec 21.
Abstract/Text BACKGROUND: After treatment for early-stage breast cancer (bca), annual surveillance mammography (asm) is recommended based on the assumption that early detection of an invasive ipsilateral breast tumour recurrence or subsequent invasive contralateral primary bca reduces bca mortality.
METHODS: We studied women with unilateral early-stage bca treated by breast-conserving surgery from 1994 to 1997 who subsequently developed an ipsilateral recurrence or contralateral primary more than 24 months after initial diagnosis, without prior regional or distant metastases. Annual surveillance mammography was defined as 2 episodes of bilateral mammography 11-18 months apart during the 2 years preceding the ipsilateral recurrence or contralateral primary. The association between asm and bca death was evaluated using a Cox proportional hazards model.
RESULTS: We identified 669 women who experienced invasive ipsilateral recurrence (n = 455) or a contralateral primary (n = 214) at a median interval of 53 months [interquartile range (iqr): 37-72 months] after initial diagnosis, 64.7% of whom had received asm during the preceding 2 years. The median interval between the 2 bilateral mammograms was 12.3 months (iqr: 11.9-13.0 months), and the median interval between the 2nd mammogram and histopathologic confirmation of ipsilateral recurrence or contralateral primary was 1.5 months (iqr: 0.8-3.9 months). Median followup after ipsilateral recurrence or contralateral primary was 7.76 years (iqr: 3.68-9.81 years). The adjusted hazard ratio for bca death associated with asm was 0.86 (95% confidence limits: 0.63, 1.16).
CONCLUSIONS: Annual surveillance mammography was associated with a modestly lowered hazard ratio for bca death.

PMID 28050142  Curr Oncol. 2016 Dec;23(6):e538-e545. doi: 10.3747/co.2・・・
著者: A Jung Chu, Jung Min Chang, Nariya Cho, Woo Kyung Moon
雑誌名: J Breast Cancer. 2017 Jun;20(2):192-197. doi: 10.4048/jbc.2017.20.2.192. Epub 2017 Jun 26.
Abstract/Text PURPOSE: The aim of our study was to investigate the characteristics of primary and recurrent breast cancers and the correlation between cancer subtypes and detection modes.
METHODS: Between 2003 and 2013, 147 cases of recurrent breast cancer in 137 women (mean age, 45.30±10.78 years) were identified via an annual clinical examination using radiological studies among 6,169 patients with a breast cancer history (mean follow-up period, 13.26±1.78 years). Clinical, radiological, and pathological findings including immunohistochemistry findings of primary and recurrent cancers were reviewed. The size of the tumor in primary and recurrent cancers, disease-free survival, methods of surgery, and the recurrence detection modalities were analyzed with respect to the breast cancer subtype.
RESULTS: Ipsilateral and contralateral in-breast recurrence occurred in 105, 21 had axillary lymph node recurrence, and 21 had chest wall recurrences. The subtypes of the primary cancers were hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative (HR+HER2-) in 57, HER2 positive (HER2+) in 39, and triple-negative type in 51, and the recurrent cancers in each subtype showed the same type as the primary cancer in 84.3% of cases. In the in-breast recurrent cancers, the HR+HER2- cancers were most frequently detected using ultrasonography (15/43) followed by mammography (MG) (11/43). The HER2+ recurrent cancers were most commonly detected using MG (14/31, 45.2%), whereas triple-negative type recurrent cancers most commonly presented as symptomatic masses (15/31) (p=0.028).
CONCLUSION: Most recurrent breast cancers showed the same cancer subtype as the primary tumor, and recurrent breast cancer subtypes correlated with the detection modality. Imaging surveillance of survivors of breast cancer might be more beneficial in cases of HR+HER2- type breast cancer or HER2+ type breast cancer than in cases of triple-negative type breast cancer.

PMID 28690656  J Breast Cancer. 2017 Jun;20(2):192-197. doi: 10.4048/j・・・
著者: Lowell E Schnipper, Thomas J Smith, Derek Raghavan, Douglas W Blayney, Patricia A Ganz, Therese Marie Mulvey, Dana S Wollins
雑誌名: J Clin Oncol. 2012 May 10;30(14):1715-24. doi: 10.1200/JCO.2012.42.8375. Epub 2012 Apr 3.
Abstract/Text
PMID 22493340  J Clin Oncol. 2012 May 10;30(14):1715-24. doi: 10.1200/・・・
著者: Irene L Wapnir, Stewart J Anderson, Eleftherios P Mamounas, Charles E Geyer, Jong-Hyeon Jeong, Elizabeth Tan-Chiu, Bernard Fisher, Norman Wolmark
雑誌名: J Clin Oncol. 2006 May 1;24(13):2028-37. doi: 10.1200/JCO.2005.04.3273.
Abstract/Text PURPOSE: Locoregional failure after breast-conserving surgery is associated with increased risk of distant disease and death. The magnitude of this risk in patients receiving chemotherapy has not been adequately characterized.
PATIENTS AND METHODS: Our study population included 2,669 women randomly assigned onto five National Surgical Adjuvant Breast and Bowel Project node-positive protocols (B-15, B-16, B-18, B-22, and B-25), who were treated with lumpectomy, whole-breast irradiation, and adjuvant systemic therapy. Cumulative incidences of ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence (oLRR) were calculated. Kaplan-Meier curves were used to estimate distant-disease-free survival (DDFS) and overall survival (OS) after IBTR or oLRR. Cox models were used to model survival using clinical and pathologic factors jointly with IBTR or oLRR as time-varying predictors.
RESULTS: Four hundred twenty-four patients (15.9%) experienced locoregional failure; 259 (9.7%) experienced IBTR, and 165 (6.2%) experienced oLRR. The 10-year cumulative incidence of IBTR and oLRR was 8.7% and 6.0%, respectively. Most locoregional failures occurred within 5 years (62.2% for IBTR and 80.6% for oLRR). Age, tumor size, and estrogen receptor status were significantly associated with IBTR. Nodal status and estrogen and progesterone receptor status were significantly associated with oLRR. The 5-year DDFS rates after IBTR and oLRR were 51.4% and 18.8%, respectively. The 5-year OS rates after IBTR and oLRR were 59.9% and 24.1%, respectively. Hazard ratios for mortality associated with IBTR and oLRR were 2.58 (95% CI, 2.11 to 3.15) and 5.85 (95% CI, 4.80 to 7.13), respectively.
CONCLUSION: Node-positive breast cancer patients who developed IBTR or oLRR had significantly poorer prognoses than patients who did not experience these events.

PMID 16648502  J Clin Oncol. 2006 May 1;24(13):2028-37. doi: 10.1200/J・・・
著者: Tracy E Alpert, Henry M Kuerer, Douglas W Arthur, Donald R Lannin, Bruce G Haffty
雑誌名: Int J Radiat Oncol Biol Phys. 2005 Nov 1;63(3):845-51. doi: 10.1016/j.ijrobp.2005.02.035.
Abstract/Text PURPOSE: To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS.
METHODS AND MATERIALS: Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size < 3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with < or = 3 positive nodes.
RESULTS: Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n = 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy.
CONCLUSIONS: While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is discussed.

PMID 16199315  Int J Radiat Oncol Biol Phys. 2005 Nov 1;63(3):845-51. ・・・
著者: John R Benson, G Querci della Rovere
雑誌名: Breast. 2008 Feb;17(1):12-18. doi: 10.1016/j.breast.2007.06.006. Epub 2008 Feb 4.
Abstract/Text The overview by the Early Breast Cancer Trialists Collaborative Group on the impact of loco-regional treatments for breast cancer on long term survival was a milestone publication which partially clarified the significance of ipsilateral breast tumour recurrence (IBTR). In the aftermath of this overview, a conference was convened in London in October 2006 to discuss various aspects of IBTR and in particular whether this represents a marker or determinant of risk for distant metastases. An international panel of speakers covered a range of issues including biological paradigms, the effect of IBTR on survival and whether surgery itself can have a detrimental effect on patient outcome. Other topics included the limits to breast conserving surgery, systemic treatments for IBTR and the role of radiotherapy in minimising IBTR. It was concluded that IBTR is a determinant of distant relapse in approximately 25% of cases and a marker of risk in 75% of cases. However, current surgical practice should not favour increased rates of mastectomy on the basis of the recent meta-analysis of randomised trials.

PMID 18249542  Breast. 2008 Feb;17(1):12-18. doi: 10.1016/j.breast.200・・・
著者: Adeyiza O Momoh, Raouf Ahmed, Brian P Kelley, Oluseyi Aliu, Kelley M Kidwell, Jeffrey H Kozlow, Kevin C Chung
雑誌名: Ann Surg Oncol. 2014 Jan;21(1):118-24. doi: 10.1245/s10434-013-3284-z. Epub 2013 Oct 1.
Abstract/Text PURPOSE: To conduct a systematic review of the literature to assess outcomes data on complications associated with implant-based breast reconstruction performed before or after chest wall radiation to assist in guiding the decision-making process for reconstruction of the irradiated breast.
METHODS: Studies from a PubMed search that met predetermined inclusion criteria were identified and included. Complications of interest were low- and high-grade capsular contractures, minor and major complications, reconstruction failure rates, and reconstruction completion rates. Pooled complication rates were calculated.
RESULTS: A total of 26 articles were included in the study after screening 1,006 publications, with 14 studies presenting data on prereconstruction radiation and 23 studies presenting data on postreconstruction radiation. Complication rates evaluated in patients exposed to radiation before or after implant reconstruction were not significantly different. Reconstruction failure rates were similar at 19 and 20 % for pre- and postreconstruction radiation patients, respectively. Completion rates were similar at 83 and 80 % for pre- and postreconstruction radiation patients, respectively.
CONCLUSIONS: Review of the current literature suggests similar overall success and failure rates with radiotherapy provided both before and after reconstruction. Failure rates in both groups of patients are clinically significant when considering implant reconstruction in the setting of radiation.

PMID 24081801  Ann Surg Oncol. 2014 Jan;21(1):118-24. doi: 10.1245/s10・・・
著者: G Vugts, A J G Maaskant-Braat, A C Voogd, Y E A van Riet, E J T Luiten, E J Th Rutgers, H J T Rutten, R M H Roumen, G A P Nieuwenhuijzen
雑誌名: Breast Cancer Res Treat. 2015 Oct;153(3):549-56. doi: 10.1007/s10549-015-3571-4. Epub 2015 Sep 10.
Abstract/Text Most patients with locally recurrent breast cancer undergo axillary lymph node dissection (ALND). However, repeat sentinel node biopsy (SNB) could provide regional nodal staging and obviate the need for standard ALND. The Sentinel Node and Recurrent Breast Cancer (SNARB) study is a Dutch nationwide registration study conducted to determine feasibility, aberrant drainage rates, and clinical consequences of repeat SNB. A total of 536 patients with locally recurrent non-metastatic breast cancer underwent lymphatic mapping and repeat SNB in 29 Dutch hospitals. A repeat sentinel node (SN) was identified in 333 of 536 patients (62.1 %) and surgically harvested in 287 patients (53.5 %). Aberrant lymph drainage was observed in 180 (54.1 %) of the 333 patients, more often after previous ALND (81.9 %) than SNB (28.4 %; P < 0.001). In 230 patients (80.1 %), the retrieved SN was tumor negative; 17 SNs (5.9 %) contained a micrometastasis and 29 (10.1 %) a macrometastasis. Confirmation ALND in 31 repeat SN-negative patients revealed a macrometastasis in two patients (6.5 %). The negative predictive value (NPV) of repeat SNB was 93.6 %, and ALND was omitted in 109 of the 248 patients (44.0 %) with a negative repeat SN. In 29 of the 44 patients (63.0 %) with a positive SN, adjuvant treatment plans were altered based on the repeat SNB. Repeat SNB is a feasible procedure with a high NPV, leading to a change in management in a substantial proportion of patients. Therefore, repeat SNB should replace routine ALND and serve as the standard of care in recurrent breast cancer.

PMID 26358709  Breast Cancer Res Treat. 2015 Oct;153(3):549-56. doi: 1・・・
著者: M Intra, G Viale, J Vila, C M Grana, A Toesca, O Gentilini, V Galimberti, P Veronesi, A Luini, N Rotmensz, V Bagnardi, D Mattar, M Colleoni
雑誌名: Ann Surg Oncol. 2015 Jul;22(7):2372-7. doi: 10.1245/s10434-014-4282-5. Epub 2014 Dec 17.
Abstract/Text PURPOSE: This retrospective study aimed to determine the feasibility, accuracy, and recurrence rates of lymphoscintigraphy and the new sentinel lymph node biopsy (SLNB) for patients with ipsilateral breast tumor recurrences who were treated previously with conservative surgery and had negative SLNB results.
METHODS: The study was conducted at the European Institute of Oncology in Milan and included 212 patients with the diagnosis of operable local breast cancer recurrence. They had been treated previously with conservative surgery and showed negative SLNB results. They subsequently underwent additional breast surgery and a second SLNB between May 2001 and December 2011.
RESULTS: Preoperative lymphoscintigraphy demonstrated at least one new axillary sentinel lymph node (SLN) in 207 patients (97.7 %), whereas no drainage was observed in five patients (2.3 %). One or more SLNs were surgically removed from 196 of the 207 patients. Isolation of SLNs from the remaining 11 patients could not be accomplished. The success rate for the SLNB was 92.5 %. Extra-axillary drainage pathways were visualized in 17 patients (8 %). The annual axillary recurrence rate after a median follow-up period of 48 months was 0.8 %, and the cumulative incidence of axillary recurrence at 5 years was 3.9 %.
CONCLUSIONS: A second SLNB should be considered for patients with operable local breast tumor recurrence who underwent conservative surgery and had negative SLNB results. The procedure is technically feasible and accurate for selected patients.

PMID 25515197  Ann Surg Oncol. 2015 Jul;22(7):2372-7. doi: 10.1245/s10・・・
著者: Yasuaki Sagara, Rachel A Freedman, Ines Vaz-Luis, Melissa Anne Mallory, Stephanie M Wong, Fatih Aydogan, Stephen DeSantis, William T Barry, Mehra Golshan
雑誌名: J Clin Oncol. 2016 Apr 10;34(11):1190-6. doi: 10.1200/JCO.2015.65.1869. Epub 2016 Feb 1.
Abstract/Text PURPOSE: Radiotherapy (RT) after breast-conserving surgery (BCS) is a standard treatment option for the management of ductal carcinoma in situ (DCIS). We sought to determine the survival benefit of RT after BCS on the basis of risk factors for local recurrence.
PATIENTS AND METHODS: A retrospective longitudinal cohort study was performed to identify patients with DCIS diagnosed between 1988 and 2007 and treated with BCS by using SEER data. Patients were divided into the following two groups: BCS+RT (RT group) and BCS alone (non-RT group). We used a patient prognostic scoring model to stratify patients on the basis of risk of local recurrence. We performed a Cox proportional hazards model with propensity score weighting to evaluate breast cancer mortality between the two groups.
RESULTS: We identified 32,144 eligible patients with DCIS, 20,329 (63%) in the RT group and 11,815 (37%) in the non-RT group. Overall, 304 breast cancer-specific deaths occurred over a median follow-up of 96 months, with a cumulative incidence of breast cancer mortality at 10 years in the weighted cohorts of 1.8% (RT group) and 2.1% (non-RT group; hazard ratio, 0.73; 95% CI, 0.62 to 0.88). Significant improvements in survival in the RT group compared with the non-RT group were only observed in patients with higher nuclear grade, younger age, and larger tumor size. The magnitude of the survival difference with RT was significantly correlated with prognostic score (P < .001).
CONCLUSION: In this population-based study, the patient prognostic score for DCIS is associated with the magnitude of improvement in survival offered by RT after BCS, suggesting that decisions for RT could be tailored on the basis of patient factors, tumor biology, and the prognostic score.

© 2016 by American Society of Clinical Oncology.
PMID 26834064  J Clin Oncol. 2016 Apr 10;34(11):1190-6. doi: 10.1200/J・・・
著者: Lawrence J Solin, Robert Gray, Frederick L Baehner, Steven M Butler, Lorie L Hughes, Carl Yoshizawa, Diana B Cherbavaz, Steven Shak, David L Page, George W Sledge, Nancy E Davidson, James N Ingle, Edith A Perez, William C Wood, Joseph A Sparano, Sunil Badve
雑誌名: J Natl Cancer Inst. 2013 May 15;105(10):701-10. doi: 10.1093/jnci/djt067. Epub 2013 May 2.
Abstract/Text BACKGROUND: For women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical excision without radiation is not well defined by clinical and pathologic characteristics.
METHODS: The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group (ECOG) E5194 study. The association of the prospectively defined DCIS Score (calculated from seven cancer-related genes and five reference genes) with the risk of developing an IBE was analyzed using Cox regression. All statistical tests were two-sided.
RESULTS: There were 327 patients with adequate tissue for analysis. The continuous DCIS Score was statistically significantly associated with the risk of developing an IBE (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.15 to 4.49; P = .02) when adjusted for tamoxifen use (prespecified primary analysis) and with invasive IBE (unadjusted HR = 3.68, 95% CI = 1.34 to 9.62; P = .01). For the prespecified DCIS risk groups of low, intermediate, and high, the 10-year risks of developing an IBE were 10.6%, 26.7%, and 25.9%, respectively, and for an invasive IBE, 3.7%, 12.3%, and 19.2%, respectively (both log rank P ≤ .006). In multivariable analyses, factors associated with IBE risk were DCIS Score, tumor size, and menopausal status (all P ≤ .02).
CONCLUSIONS: The DCIS Score quantifies IBE risk and invasive IBE risk, complements traditional clinical and pathologic factors, and provides a new clinical tool to improve selecting individualized treatment for women with DCIS who meet the ECOG E5194 criteria.

PMID 23641039  J Natl Cancer Inst. 2013 May 15;105(10):701-10. doi: 10・・・
著者: Melinda E Sanders, Peggy A Schuyler, William D Dupont, David L Page
雑誌名: Cancer. 2005 Jun 15;103(12):2481-4. doi: 10.1002/cncr.21069.
Abstract/Text BACKGROUND: Opportunities to study the natural history of ductal carcinoma in situ (DCIS) are rare. A few studies of incompletely excised lesions in the premammographic era now recognized as DCIS have provided critical insights into its proclivity for local recurrence in the original site. At the time the biopsies in the current study were originally examined, small DCIS was not diagnosed and, by default, these women were treated by biopsy only.
METHODS: The authors report the latest results from a follow-up study, which was published originally in 1982, of 28 women with low-grade DCIS who were treated by biopsy only. These women were from a large, prospectively identified, completely characterized cohort.
RESULTS: Eleven of 28 women developed invasive breast carcinoma (IBC), all in the same breast and quadrant from which their low-grade DCIS biopsy was taken. Seven IBCs were diagnosed within 10 years of the DCIS biopsy, 1 was diagnosed within 12 years of the DCIS biopsy, and the remaining 3 IBCs were diagnosed over 23-42 years. Five of these women, including 1 woman who developed IBC 29 years after her DCIS biopsy, developed distant metastasis, which resulted in death 1-7 years after the diagnosis of IBC.
CONCLUSIONS: The natural history of low-grade DCIS can extend greater than 4 decades, with IBC developing at the same site as the previous DCIS in the majority of women. This natural history differs markedly from that of patients with high-grade DCIS and from the outcome of patients with any completely delimited DCIS excised to negative margins.

Copyright 2005 American Cancer Society.
PMID 15884091  Cancer. 2005 Jun 15;103(12):2481-4. doi: 10.1002/cncr.2・・・
著者: N Bijker, J L Peterse, L Duchateau, E C Robanus-Maandag, C A Bosch, C Duval, S Pilotti, M J van de Vijver
雑誌名: Br J Cancer. 2001 Feb;84(4):539-44. doi: 10.1054/bjoc.2000.1618.
Abstract/Text We have investigated primary ductal carcinomas in situ (DCIS) of the breast and their local recurrences after breast-conserving therapy (BCT) for histological characteristics and marker expression. Patients who were randomized in the EORTC trial 10853 (wide local excision versus excision plus radiotherapy) and who developed a local recurrence were identified. Histology was reviewed for 116 cases; oestrogen and progesterone receptor status, and HER2/ neu and p53 overexpression were assessed for 71 cases. Comparing the primary DCIS and the invasive or non-invasive recurrence, concordant histology was found in 62%, and identical marker expression in 63%. Although 11% of the recurrences developed at a distance from the primary DCIS, nearly all these showed the same histological and immunohistochemical profile. 5 patients developed well-differentiated DCIS or grade I invasive carcinoma after poorly differentiated DCIS. Although these recurrences occurred in the same quadrant as the primary DCIS, they may be considered as second primary tumours. Only 4 patients developed poorly differentiated DCIS or grade III invasive carcinoma after well differentiated DCIS. We conclude that in most cases the primary DCIS and its local recurrence are related histologically or by marker expression, suggesting that local recurrence usually reflects outgrowth of residual DCIS; progression of well differentiated DCIS towards poorly differentiated DCIS or grade III invasive carcinoma is a non-frequent event.

Copyright 2001 Cancer Research Campaign.
PMID 11207051  Br J Cancer. 2001 Feb;84(4):539-44. doi: 10.1054/bjoc.2・・・
著者: M Luke Marinovich, Lamiae Azizi, Petra Macaskill, Les Irwig, Monica Morrow, Lawrence J Solin, Nehmat Houssami
雑誌名: Ann Surg Oncol. 2016 Nov;23(12):3811-3821. doi: 10.1245/s10434-016-5446-2. Epub 2016 Aug 15.
Abstract/Text PURPOSE: There is no consensus on adequate negative margins in breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We systematically reviewed the evidence on margins in BCS for DCIS.
METHODS: A study-level meta-analysis of local recurrence (LR), microscopic margin status and threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression (frequentist) and network meta-analysis (Bayesian) that allows for multiple margin distances per study, adjusting for follow-up time.
RESULTS: Based on 20 studies (LR: 865 of 7883), odds of LR were associated with margin status [logistic: odds ratio (OR) 0.53 for negative vs. positive/close (p < 0.001); network: OR 0.45 for negative vs. positive]. In logistic meta-regression, relative to >0 or 1 mm, ORs for 2 mm (0.51), 3 or 5 mm (0.42) and 10 mm (0.60) showed comparable significant reductions in the odds of LR. In the network analysis, ORs relative to positive margins for 2 (0.32), 3 (0.30) and 10 mm (0.32) showed similar reductions in the odds of LR that were greater than for >0 or 1 mm (0.45). There was weak evidence of lower odds at 2 mm compared with >0 or 1 mm [relative OR (ROR) 0.72, 95 % credible interval (CrI) 0.47-1.08], and no evidence of a difference between 2 and 10 mm (ROR 0.99, 95 % CrI 0.61-1.64). Adjustment for covariates, and analyses based only on studies using whole-breast radiotherapy, did not change the findings.
CONCLUSION: Negative margins in BCS for DCIS reduce the odds of LR; however, minimum margin distances above 2 mm are not significantly associated with further reduced odds of LR in women receiving radiation.

PMID 27527715  Ann Surg Oncol. 2016 Nov;23(12):3811-3821. doi: 10.1245・・・
著者: Monica Morrow, Kimberly J Van Zee, Lawrence J Solin, Nehmat Houssami, Mariana Chavez-MacGregor, Jay R Harris, Janet Horton, Shelley Hwang, Peggy L Johnson, M Luke Marinovich, Stuart J Schnitt, Irene Wapnir, Meena S Moran
雑誌名: J Clin Oncol. 2016 Nov 20;34(33):4040-4046. doi: 10.1200/JCO.2016.68.3573. Epub 2016 Oct 31.
Abstract/Text Background Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation (WBRT). Methods A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus. Results Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2 mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2 mm margins. Negative margins less than 2 mm alone are not an indication for mastectomy, and factors known to impact rates of IBTR should be considered in determining the need for re-excision. Conclusion The use of a 2 mm margin as the standard for an adequate margin in DCIS treated with WBRT is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcome, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins < 2 mm.

PMID 27528719  J Clin Oncol. 2016 Nov 20;34(33):4040-4046. doi: 10.120・・・
著者: Judith Berbers, Angela van Baardwijk, Ruud Houben, Esther Heuts, Marjolein Smidt, Kristien Keymeulen, Maud Bessems, Stefania Tuinder, Liesbeth J Boersma
雑誌名: Eur J Cancer. 2014 Nov;50(16):2752-62. doi: 10.1016/j.ejca.2014.07.023. Epub 2014 Aug 26.
Abstract/Text OBJECTIVE: The aim of this review is to investigate the effect of timing of the reconstruction and radiotherapy, with respect to complication rate and cosmetic outcome, with a special focus on the timing of the placement of the definite implant.
METHODS: PubMed was searched for publications between January 2000 and December 2012. Of 37 eligible studies, timing of reconstruction, type, and incidence of complications were recorded. First, we calculated the weighted mean including confidence intervals for complications and cosmetic outcome overall, and for the following subgroups: (1) Autologous reconstruction after radiotherapy; (2) Definite implant reconstruction after radiotherapy; (3) Autologous reconstruction before radiotherapy; (4) Definite implant reconstruction before radiotherapy. A second analysis was performed using only studies that directly compared group 1 versus 3 and 2 versus 4.
RESULTS: A large variation in complication rates (8.7-70.0%) and in acceptable cosmetic outcome (41.4-93.3%) was reported. The first analysis showed more complications and a higher revision rate if an implant reconstruction was performed after radiotherapy; for autologous reconstruction fibrosis occurred more often if reconstruction was applied first. The second analysis showed no significant differences in total complication rate. Only implant failure occurred more often if applied after radiotherapy (odds ratio (OR) 3.03 [1.59-5.77]). No differences were found in both patient and physician satisfaction.
CONCLUSIONS: A definite implant reconstruction placed before radiotherapy limits the rate of complications. For autologous reconstruction, less fibrosis is seen if reconstruction is performed after radiotherapy, but timing had no significant impact on total complication rate.

Copyright © 2014 Elsevier Ltd. All rights reserved.
PMID 25168640  Eur J Cancer. 2014 Nov;50(16):2752-62. doi: 10.1016/j.e・・・
著者: Kyeong-Tae Lee, Goo-Hyun Mun
雑誌名: J Surg Oncol. 2015 Oct;112(5):468-75. doi: 10.1002/jso.24032. Epub 2015 Sep 16.
Abstract/Text BACKGROUND AND OBJECTIVES: The present review evaluated the impacts of pre-reconstruction radiotherapy on outcome of prosthetic breast reconstruction and compared the safety of prosthetic reconstruction with that of other modalities, including autologous tissue reconstruction and the combination of flap and implant in the setting of pre-reconstruction radiation.
METHODS: Studies presenting outcomes of prosthetic breast reconstruction in the setting of pre-reconstruction radiation published in the past 10 years were identified and reviewed.
RESULTS: Twenty studies were analyzed. Prosthetic reconstruction in previously irradiated breasts showed significantly increased risks for complications, including reconstruction failure (relative risk, 2.58; 95% confidence interval, 1.86-3.57) than those cases without radiation, regardless of the specific surgical technique used, including one-/two-stage reconstruction, use of an acellular dermal matrix or not, and the timing of the reconstruction (immediate/delayed). Autologous tissue reconstruction and a combination flap and implant showed a 92% and 72% decreased risk of reconstruction failure, respectively, in previously irradiated breasts compared with that of prosthetic reconstruction.
CONCLUSIONS: The results suggest that prior irradiation significantly increases the risk of complications in patients undergoing prosthetic reconstruction, and using an autologous flap or combining it with an implant can be considered to reconstruct previously irradiated breasts.

© 2015 Wiley Periodicals, Inc.
PMID 26374273  J Surg Oncol. 2015 Oct;112(5):468-75. doi: 10.1002/jso.・・・
著者: Fredrik Wärnberg, Hans Garmo, Stefan Emdin, Veronica Hedberg, Linda Adwall, Kerstin Sandelin, Anita Ringberg, Per Karlsson, Lars-Gunnar Arnesson, Harald Anderson, Karin Jirström, Lars Holmberg
雑誌名: J Clin Oncol. 2014 Nov 10;32(32):3613-8. doi: 10.1200/JCO.2014.56.2595. Epub 2014 Oct 13.
Abstract/Text PURPOSE: Four randomized studies show that adjuvant radiotherapy (RT) lowers the risk of subsequent ipsilateral breast events (IBEs) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) by approximately 50% after 10 to 15 years. We present 20 years of follow-up data for the SweDCIS trial.
PATIENTS AND METHODS: Between 1987 and 1999 1,046 women were randomly assigned to RT or not after BCS for primary DCIS. Results up to 2005 have been published, and we now add another 7 years of follow-up. All breast cancer events and causes of death were registered.
RESULTS: There were 129 in situ and 129 invasive IBEs. Absolute risk reduction in the RT arm was 12.0% at 20 years (95% CI, 6.5 to 17.7), with a relative risk reduction of 37.5%. Absolute reduction was 10.0% (95% CI, 6.0 to 14.0) for in situ and 2.0% (95% CI, -3.0 to 7.0) for invasive IBEs. There was a nonstatistically significantly increased number of contralateral events in the RT arm (67 v 48 events; hazard ratio, 1.38; 95% CI, 0.95 to 2.00). Breast cancer-specific death and overall survival were not influenced. Younger women experienced a relatively higher risk of invasive IBE and lower effect of RT. The hazard over time looked different for in situ and invasive IBEs.
CONCLUSION: Use of adjuvant RT is supported by 20-year follow-up. Modest protection against invasive recurrences and a possible increase in contralateral cancers still call for a need to find groups of patients for whom RT could be avoided or mastectomy with breast reconstruction is indicated.

© 2014 by American Society of Clinical Oncology.
PMID 25311220  J Clin Oncol. 2014 Nov 10;32(32):3613-8. doi: 10.1200/J・・・

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契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから