Fredika M Robertson, Melissa Bondy, Wei Yang, Hideko Yamauchi, Shannon Wiggins, Samira Kamrudin, Savitri Krishnamurthy, Huong Le-Petross, Luc Bidaut, Audrey N Player, Sanford H Barsky, Wendy A Woodward, Thomas Buchholz, Anthony Lucci, Naoto T Ueno, Naoto Ueno, Massimo Cristofanilli
Inflammatory breast cancer: the disease, the biology, the treatment.
CA Cancer J Clin. 2010 Nov-Dec;60(6):351-75. doi: 10.3322/caac.20082. Epub 2010 Oct 19.
Abstract/Text
Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, younger age of onset, and lower overall survival compared with other breast cancers. Historically, IBC is a lethal disease with less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy. Because of its rarity, IBC is often misdiagnosed as mastitis or generalized dermatitis. This review examines IBC's unique clinical presentation, pathology, epidemiology, imaging, and biology and details current multidisciplinary management of the disease, which comprises systemic therapy, surgery, and radiation therapy.
© 2010 American Cancer Society, Inc.
Taylor G, Meltzer A: Inflammatory carcinoma of the Breast. Am J Cancer 33:33-49, 1938.
D L Ellis, S L Teitelbaum
Inflammatory carcinoma of the breast. A pathologic definition.
Cancer. 1974 Apr;33(4):1045-7.
Abstract/Text
P Bonnier, S Romain, C Charpin, C Lejeune, N Tubiana, P M Martin, L Piana
Age as a prognostic factor in breast cancer: relationship to pathologic and biologic features.
Int J Cancer. 1995 Jul 17;62(2):138-44.
Abstract/Text
The relationship of age with prognostic factors and outcome of breast cancer has long been controversial due to numerous confounding factors. In order to clarify the prognostic value of age, we analyzed a homogeneous population of 1,266 patients treated for breast cancer at the same institution (mean follow-up: 62 months). Three groups were compared: patients under 35 years of age, non-menopausal patients over 35 years of age, and post-menopausal patients under the age of 70 years. A higher frequency of undifferentiated tumors, histoprognostic grade-3 cancer, microscopic lymph-node involvement and negative hormonal receptor status was observed in patients under 35 years. In addition, clinical but not anatomical tumor size was greater in young patients, suggesting higher stromal activity. Metastasis-free survival and overall survival were significantly poorer before 35 years. Differences were observed when patients were matched with regard to stage, anatomic size, histoprognostic grade, microscopic lymph-node involvement and receptor status. Multivariate analysis of both overall and metastasis-free survival demonstrated that age younger than 35 years was an independent risk factor. Younger women had a higher risk of local recurrence but, unlike older women, they did not experience any worsening of the already unfavorable outcome due to recurrence.
N T Ueno, A U Buzdar, S E Singletary, F C Ames, M D McNeese, F A Holmes, R L Theriault, E A Strom, B J Wasaff, L Asmar, D Frye, G N Hortobagyi
Combined-modality treatment of inflammatory breast carcinoma: twenty years of experience at M. D. Anderson Cancer Center.
Cancer Chemother Pharmacol. 1997;40(4):321-9. doi: 10.1007/s002800050664.
Abstract/Text
PURPOSE: To review the 20 years of experience at M. D. Anderson Cancer Center with a combined-modality approach against inflammatory breast carcinoma.
PATIENTS AND METHODS: A total of 178 patients with inflammatory breast carcinoma were treated in the past 20 years at M. D. Anderson Cancer Center by a combined-modality approach under four different protocols. Each protocol included induction chemotherapy, then local therapy (radiotherapy or mastectomy), then adjuvant chemotherapy, and, if mastectomy was performed, adjuvant radiotherapy. Chemotherapy consisted of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) with or without vincristine and prednisone (VP). In protocol D, patients received an alternate adjuvant chemotherapy regimen, methotrexate and vinblastine (MV), if they did not have a complete response (CR) to induction chemotherapy.
RESULTS: The median follow-up of live patients in group A was 215 months, in group B 186 months, in group C 116 months, and in group D 45 months. An estimated 28% of patients were currently free of disease beyond 15 years. At the time of analysis, 50 patients were alive without any evidence of disease. A further 12 patients died of intercurrent illness, and 15 patients were followed beyond 10 years without recurrence of disease. Among initial recurrence, 20% of patients had local failure, 39% systemic failure, and 9% CNS recurrence. Initial response to induction chemotherapy was an important prognostic factor. Disease-free survival (DFS) at 15 years was 44% in patients who had a CR to induction chemotherapy, 31% in those who had a partial response (PR), and 7% in those who had less than a PR. There was no improvement in overall survival (OS) or DFS among patients who underwent alternate chemotherapy (MV) compared with those who did not. Using surgery and radiotherapy as opposed to radiotherapy alone as local therapy did not have an impact on the DFS or OS rate.
CONCLUSION: These long-term follow-up data show that with a combined-modality approach a significant fraction of patients (28%) remained free of disease beyond 15 years. In contrast, single-modality treatments yielded a DFS of less than 5%. Thus, using combined-modality treatment (chemotherapy, then mastectomy, then chemotherapy and radiotherapy) is recommended as a standard of care for inflammatory breast carcinoma.
C C Lamb, T J Eberlein, L M Parker, B Silver, J R Harris
Results of radical radiotherapy for inflammatory breast cancer.
Am J Surg. 1991 Sep;162(3):236-42.
Abstract/Text
We performed a retrospective review of 65 patients with nonmetastatic clinical inflammatory breast carcinoma treated with radical radiotherapy as the sole local treatment between 1968 and 1986. Chemotherapy was given to 47 patients (72%). The median total radiation dose to the target volume was 6,984 cGy. With a median follow-up in survivors of 41 months, the 5-year actuarial probability of relapse-free survival was 17% and the overall survival was 28%. Thirty patients experienced failure in the treated breast, skin, or draining lymph nodes, for a crude, uncensored local recurrence rate of 46%. Of the factors analyzed, only the response to initial chemotherapy was predictive of local recurrence. Local recurrence was noted in 0 of 3 patients with a complete response (CR) to initial chemotherapy, 5 of 17 patients with a partial response (PR), and 12 of 17 patients with less than a partial response (CR/PR versus less than PR, p = 0.009). We conclude that conventional radical radiotherapy in unselected patients is insufficient to manage the local tumor burden presented by inflammatory breast cancer, even when high doses are employed.
Malcolm R Kell, Monica Morrow
Surgical aspects of inflammatory breast cancer.
Breast Dis. 2005-2006;22:67-73.
Abstract/Text
Mastectomy alone as a treatment for inflammatory breast cancer results in local recurrence in 20% of cases and a median survival of only 2 years. Current management of inflammatory cancer employs initial chemotherapy with surgery reserved for patients who have complete resolution of inflammatory changes. The combination of chemotherapy, mastectomy, and radiotherapy results in local control in 80% of patients. Breast conserving surgery and sentinel node biopsy are contraindicated in inflammatory cancer.
Haagensen C: Inflammatory carcinoma, Disease of the Breast. Philadelphia, PA, W. B. Saunders, 1971, pp 576-584.
F Bozzetti, R Saccozzi, M De Lena, B Salvadori
Inflammatory cancer of the breast: analysis of 114 cases.
J Surg Oncol. 1981;18(4):355-61.
Abstract/Text
One hundred and fourteen cases of inflammatory breast cancer were reviewed. Actuarial survival curves, independent of the stage and type of treatment, showed a median survival of less than 15 months. As regards the three different subgroups of 80, 14, and 20 women, N0-1-2M0, N3M1 respectively, the acutuarial survival curves showed figures of median survival that decreased from 14 to 4 months, according to the extent of the disease. Survival rates for the subgroups of patients treated by radical mastectomy, radical mastectomy followed by radiotherapy, and radiotherapy alone were not significantly different. Neither the more sophisticated therapeutic approaches intended to modify the hormonal medium of the patients, nor the combined chemotherapy plus radiotherapy, proved to be successful. Inflmmatory breast cancer should be considered a systemic disease; consequently, in spite of discouraging results, only a systemic therapeutic approach, consisting of aggressive combination chemotherapy and perhaps immunostimulation, seems worthwhile.
Jennifer A Low, Arlene W Berman, Seth M Steinberg, David N Danforth, Marc E Lippman, Sandra M Swain
Long-term follow-up for locally advanced and inflammatory breast cancer patients treated with multimodality therapy.
J Clin Oncol. 2004 Oct 15;22(20):4067-74. doi: 10.1200/JCO.2004.04.068.
Abstract/Text
PURPOSE: To determine long-term event-free (EFS) and overall survival (OS) for patients with stage III breast cancer treated with combined-modality therapy.
PATIENTS AND METHODS: Between 1980 and 1988, 107 patients with stage III breast cancer were prospectively enrolled for study at the National Cancer Institute and stratified by whether or not they had features of inflammatory breast cancer (IBC). Patients were treated to best response with cyclophosphamide, doxorubicin, methotrexate, fluorouracil, leucovorin, and hormonal synchronization with conjugated estrogens and tamoxifen. Patients with pathologic complete response received definitive radiotherapy to the breast and axilla, whereas patients with residual disease underwent mastectomy, lymph node dissection, and radiotherapy. All patients underwent six additional cycles of adjuvant chemotherapy.
RESULTS: OS and EFS were obtained with a median live patient follow-up time of 16.8 years. The 46 IBC patients had a median OS of 3.8 years and EFS of 2.3 years, compared with 12.2 and 9.0 years, respectively, in stage IIIA breast cancer patients. Fifteen-year OS survival was 20% for IBC versus 50% for stage IIIA patients and 23% for stage IIIB non-IBC. Pathologic response was not associated with improved survival for stage IIIA or IBC patients. Presence of dermal lymphatic invasion did not change the probability of survival in clinical IBC patients.
CONCLUSION: Fifteen-year follow-up of stage IIIA and inflammatory breast cancer is rarely reported; IBC patients have a poor long-term outlook.
Editta Baldini, Giovanni Gardin, Giuseppe Evagelista, Tiziana Prochilo, Paola Collecchi, Rita Lionetto
Long-term results of combined-modality therapy for inflammatory breast carcinoma.
Clin Breast Cancer. 2004 Dec;5(5):358-63.
Abstract/Text
Sixty-eight patients with inflammatory breast carcinoma (IBC) received treatment in 2 prospective randomized trials of multimodality therapy for locally advanced breast cancer. The treatment plan consisted of 3 courses of neoadjuvant chemotherapy with CAF (cyclophosphamide/doxorubicin/5-fluorouracil [5-FU]) or CEF (cyclophosphamide/epirubicin/5-FU) followed by surgery and 6 adjuvant courses of CAF or CEF alternated with CMF (cyclophosphamide/methotrexate/5-FU). Radiation therapy was administered at the end of adjuvant treatment. All patients with estrogen receptor-positive tumors received tamoxifen 20 mg daily for 5 years. The response rate to induction chemotherapy was 73.6% (95% CI, 61.4%-83.5%): 4 of 68 patients (6%) exhibited a pathologic remission of primary breast tumor (persistent disease in the axilla), and 2 patients (3%) exhibited a pathologic complete response. Median follow-up was 10 years (range, 5 months to 14.7 years). Disease-free survival (DFS) rates at 5 and 10 years were 29% and 20%, respectively, and median DFS was 2.2 years (range, 3.8 months to 11.5 years). Overall survival (OS) rates at 5 and 10 years were 44% and 32%, respectively, and median OS was 4 years (range, 5 months to 14.7 years). Significant prognostic factors for DFS and OS were the number of axillary nodes and residual disease in the breast at surgery. This analysis confirmed that patients with IBC obtained significant long-term survival benefit from combined-modality therapy.
Eleanor E R Harris, Delray Schultz, Helaine Bertsch, Kevin Fox, John Glick, Lawrence J Solin
Ten-year outcome after combined modality therapy for inflammatory breast cancer.
Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1200-8.
Abstract/Text
PURPOSE: To evaluate the long-term outcome of combined modality therapy for inflammatory breast cancer.
METHODS AND MATERIALS: The data from 54 women treated between 1983 and 1996 for inflammatory breast cancer were analyzed. Patients with metastatic disease or disease progression on induction chemotherapy were excluded. Induction chemotherapy was given to 52 patients. Mastectomy was performed in 52 patients. Radiotherapy was delivered to the breast or chest wall and regional lymph nodes in all patients. The median follow-up for all patients was 5.1 years.
RESULTS: The 5- and 10-year overall survival rate was 56% and 35%, respectively; the corresponding relapse-free survival rates were 49% and 34%. Patients with a pathologic complete response after chemotherapy with or without preoperative radiotherapy had better 5- and 10-year overall survival rates (65% and 46%, respectively) and 5- and 10-year relapse-free survival rates (59% and 50%, respectively) compared with patients without a pathologic complete response. Those patients had a 5- and 10-year relapse-free survival rate of 45% and 27%, respectively. Locoregional failure at 5 and 10 years was 8% and 19%, respectively.
CONCLUSION: The outcomes for patients completing multimodality therapy compare favorably with published data; however, the exclusion of patients with progression during induction chemotherapy may account in part for these results. The pathologic complete response rate was found to be an important prognostic factor. Selected patients with inflammatory breast cancer have the potential for long-term survival.
R L Bauer, E Busch, E Levine, S B Edge
Therapy for inflammatory breast cancer: impact of doxorubicin-based therapy.
Ann Surg Oncol. 1995 Jul;2(4):288-94.
Abstract/Text
BACKGROUND: Inflammatory breast cancer (IBC) carries an ominous prognosis. Before 1988, women with IBC at our institution were treated with neoadjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with or without vincristine and prednisone (CMF/VP). After 1988, women with IBC were treated with cyclophosphamide, doxorubicin, and 5-fluorouracil (FAC). This study compares these two regimens with regard to response and survival.
METHODS: The records of all women presenting between January 1973 and December 1991 with a stage IIIB (T4d, any N, MO) breast cancer with proven dermal lymphatic invasion by tumor cells were reviewed retrospectively.
RESULTS: The study comprised 38 women; 28 received CMF (22 CMF, 6 CMF/VP), and 10 received FAC. The overall response rate to induction chemotherapy in the CMF/VP group was 57% (40% PR, 17% CR), and 100% (60% PR, 40% CR) in the FAC group. The median overall survival for women receiving CMF/VP was 18 months compared with 30 months for women receiving FAC (p = 0.02). The median disease-free survivals for the CMF/VP and FAC groups were 6 and 24 months, respectively (p < 0.001). When comparing responders and nonresponders with CMF/VP induction therapy, the responders had a significantly longer overall median survival (24 versus 10 months) (p < 0.001) and disease-free median survival (8 versus 2 months) (p < 0.001). All of the five patients remaining alive received FAC with 80% (four of five) having a complete response. These four patients subsequently underwent mastectomy and radiation.
CONCLUSION: This study suggests that a doxorubicin-containing chemotherapy regimen improves overall and disease-free median survivals when compared with the previously used CMF combination in the treatment of IBC. A favorable response to induction chemotherapy also appeared to be associated with an improved survival.
Serban Dan Costa, Sibylle Loibl, Manfred Kaufmann, Dirk-Michael Zahm, Jörn Hilfrich, Jens Huober, Holger Eidtmann, Andreas du Bois, Jens-Uwe Blohmer, Beyhan Ataseven, Erich Weiss, Hans Tesch, Bernd Gerber, Klaus H Baumann, Christoph Thomssen, Georg Peter Breitbach, Shaip Ibishi, Christian Jackisch, Keyur Mehta, Gunter von Minckwitz
Neoadjuvant chemotherapy shows similar response in patients with inflammatory or locally advanced breast cancer when compared with operable breast cancer: a secondary analysis of the GeparTrio trial data.
J Clin Oncol. 2010 Jan 1;28(1):83-91. doi: 10.1200/JCO.2009.23.5101. Epub 2009 Nov 9.
Abstract/Text
PURPOSE Neoadjuvant chemotherapy followed by mastectomy is the treatment of choice in patients with inflammatory breast cancer (IBC) or locally advanced breast cancer (LABC), but it is considered less effective in these diseases than in operable breast cancer (OBC). We report a prospective comparison of the GeparTrio trial of patients with IBC (cT4 days) or LABC (cT4a-c or cN3; stage IIIB or IIIC) and patients with OBC (cT2-3). PATIENTS AND METHODS Participants were stratified by stage and were randomly assigned to six or eight cycles of docetaxel/doxorubicin/cyclophosphamide (TAC) or to two cycles of TAC followed by four cycles of vinorelbine/capecitabine. We present results of a secondary aim of the study, which was to compare pathologic complete response (pCR; ie, no remaining invasive/noninvasive tumor in breast and lymph nodes) in different stage groups. Results A total of 287 patients with IBC (n = 93) or LABC (n = 194) and 1,777 patients with OBC were entered onto the trial. At baseline, parameters were as follows for the three types of cancer, respectively: median tumor sizes: 8.0 cm, 7.0 cm, and 4.0 cm (P < .001); multiple lesions: 31.2%, 27.3%, and 19.6% (P < .001); nodal involvement: 86.6%, 71.2%, and 51.6% (P < .001); grade 3: 44.4%, 30.4%, and 39.9% (P = .178); lobular-invasive type: 7.5%, 17.5%, and 13.3% (P = .673); negative hormone receptor status: 38.0%, 20.0%, and 36.4% (P = .008); and positive human growth factor receptor 2 status: 45.1%, 38.9%, and 35.7% (P = .158). Response rates for IBC, LABC, and OBC, respectively, were 8.6%, 11.3%, and 17.7% for pCR (P = .002); 71.0%, 69.6%, and 83.4% for overall response by physical or sonographic examination (P < .001); and 12.9%, 33.0%, and 69.9% for breast conservation (P < .001). All P values were for IBC and LABC versus OBC. However, tumor stage itself was not an independent predictor for pCR in multivariable analysis (odds ratio, 1.51; 95% CI, 0.88 to 2.59; P = .13). CONCLUSION No evidence of a difference in response to neoadjuvant chemotherapy was found by tumor stage when analysis was adjusted for baseline characteristics.
Bryan T Hennessy, Ana Maria Gonzalez-Angulo, Gabriel N Hortobagyi, Massimo Cristofanilli, Shu Wan Kau, Kristine Broglio, Bruno Fornage, S Eva Singletary, Aysegul Sahin, Aman U Buzdar, Vicente Valero
Disease-free and overall survival after pathologic complete disease remission of cytologically proven inflammatory breast carcinoma axillary lymph node metastases after primary systemic chemotherapy.
Cancer. 2006 Mar 1;106(5):1000-6. doi: 10.1002/cncr.21726.
Abstract/Text
BACKGROUND: Breast carcinoma axillary lymph node (ALN) pathologic complete response (pCR) after primary chemotherapy is associated with significantly higher recurrence-free survival (RFS) and overall survival (OS) rates. The purpose of the current study was to determine long-term outcome in patients achieving a pCR of cytologically proven inflammatory breast carcinoma ALN metastases after primary chemotherapy.
METHODS: Patients with cytologically documented ALN metastases from inflammatory breast carcinoma were treated in three prospective primary chemotherapy trials. After surgery, patients were subdivided into those patients with and those patients without residual ALN carcinoma. Survival was calculated using the Kaplan-Meier method.
RESULTS: Of 175 patients treated, 61 had cytologically confirmed ALN metastases. Fourteen patients (23%) achieved a pCR of the ALNs after primary chemotherapy. The 5-year OS and RFS rates were found to be improved in those patients achieving a pCR of the ALNs (82.5% [95% confidence interval (95% CI), 62.8-100%] and 78.6% [95%CI, 59.8-100%], respectively, vs. 37.1% [95%CI, 25.4-54.2%] and 25.4% [95%CI, 15.5-41.5%], respectively) (P = 0.01 [for OS] and P = 0.001 [for RFS]). Combination anthracycline and taxane-based primary chemotherapy resulted in significantly more patients achieving an ALN pCR (45% vs. 16%; P = 0.01).
CONCLUSIONS: pCR of ALN metastases is associated with an excellent prognosis in patients with inflammatory breast carcinoma. The rates of ALN pCR are nearly 50% in patients with inflammatory breast carcinoma who are treated with anthracyclines and weekly paclitaxel before surgery. However, those patients with residual ALN disease at the time of surgery greatly require the introduction of novel therapeutic strategies.
Massimo Cristofanilli, Ana Maria Gonzalez-Angulo, Aman U Buzdar, Shu-Wan Kau, Debbie K Frye, Gabriel N Hortobagyi
Paclitaxel improves the prognosis in estrogen receptor negative inflammatory breast cancer: the M. D. Anderson Cancer Center experience.
Clin Breast Cancer. 2004 Feb;4(6):415-9.
Abstract/Text
The treatment of inflammatory breast cancer includes preoperative anthracycline-based chemotherapy, surgery, and radiation therapy. In the past few years, taxanes, mainly paclitaxel, have been frequently used for preoperative chemotherapy, usually in sequence with anthracyclines. The purpose of this retrospective analysis was to determine how adding paclitaxel to anthracycline-based regimens affects prognosis. A total of 240 patients treated in 6 consecutive trials between 1973 and 2000 were included in the analysis. Group 1 (N = 178) consisted of patients treated in the first 4 trials (1973-1993) with FAC (5-fluorouracil/doxorubicin/cyclophosphamide) based regimens. Group 2 (N = 62) consisted of patients treated in the last 2 trials (1994-2000) with FAC followed by paclitaxel given every 3 weeks or given in a high-dose weekly schedule. The 2 groups differed with respect to median follow-up durations, which were 148 months (range, 85-283 months) in group 1 and 45 months (range, 21-99 months) in group 2. Estrogen receptor (ER) status was negative in 58 cases (33%) in group 1 and 40 cases (65%) in group 2. There was no difference in median age between the groups. The objective response rates (complete and partial) were similar (group 1, 74%; group 2, 82%). The median overall survival (OS) and progression-free survival (PFS) were better in the patients treated with paclitaxel, and these differences reached statistical significance in the patients with ER-negative disease (median OS: group 1, 32 months; group 2, 54 months; P = 0.03; median PFS: group 1, 18 months; group 2, 27 months; P = 0.04). It may be concluded that the addition of paclitaxel to anthracycline-based therapy resulted in a statistically significant improvement in outcome in patients with ER-negative inflammatory breast cancer.
M Cristofanilli, A U Buzdar, N Sneige, T Smith, B Wasaff, N Ibrahim, D Booser, E Rivera, J L Murray, V Valero, N Ueno, E S Singletary, K Hunt, E Strom, M McNeese, C Stelling, G N Hortobagyi
Paclitaxel in the multimodality treatment for inflammatory breast carcinoma.
Cancer. 2001 Oct 1;92(7):1775-82.
Abstract/Text
BACKGROUND: Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast carcinoma. Anthracycline-based regimens represent the standard of treatment for IBC. Reports of significant clinical activity of paclitaxel in metastatic breast carcinoma led the authors to investigate the role of this drug in the management of IBC.
METHODS: Forty-four patients with IBC were enrolled between February 1994 and January 1998. The treatment plan consisted of induction chemotherapy (IC), mastectomy, adjuvant chemotherapy, and radiotherapy. Forty-two patients received IC with four cycles of fluorouracil, doxorubicin, and cyclophosphamide. If the clinical response was less than partial, patients were "crossed over" to paclitaxel before mastectomy. All patients received adjuvant paclitaxel. Patients unresectable after paclitaxel were offered high-dose chemotherapy with autologous peripheral blood progenitor cell support.
RESULTS: Thirty-four patients (81%) achieved an objective clinical remission; 3 patients (7%) achieved a clinical complete remission, 31 (74%) a partial remission. Six patients (14%) achieved pathologic complete remission. Sixteen patients were treated with paclitaxel, 7 of them (44%) were able to undergo mastectomy. Median time to progression (TTP) was 22 months. Median overall survival (OS) was 46 months. Concordance between clinical and pathologic response was documented in only 8 patients (24%). No differences in TTP and OS compared with a historical group of 178 IBC patients treated with anthracycline-based regimens.
CONCLUSIONS: Paclitaxel improves tumor resectability in anthracycline-refractory IBC. The impact of paclitaxel on the prognosis of IBC needs to be better evaluated in future trials using more dose-intensive schedules of administration. New imaging modalities may contribute to improve assessment of response to IC.
Copyright 2001 American Cancer Society.
S Dawood, S D Merajver, P Viens, P B Vermeulen, S M Swain, T A Buchholz, L Y Dirix, P H Levine, A Lucci, S Krishnamurthy, F M Robertson, W A Woodward, W T Yang, N T Ueno, M Cristofanilli
International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment.
Ann Oncol. 2011 Mar;22(3):515-23. doi: 10.1093/annonc/mdq345. Epub 2010 Jul 5.
Abstract/Text
BACKGROUND: Inflammatory breast cancer (IBC) represents the most aggressive presentation of breast cancer. Women diagnosed with IBC typically have a poorer prognosis compared with those diagnosed with non-IBC tumors. Recommendations and guidelines published to date on the diagnosis, management, and follow-up of women with breast cancer have focused primarily on non-IBC tumors. Establishing a minimum standard for clinical diagnosis and treatment of IBC is needed.
METHODS: Recognizing IBC to be a distinct entity, a group of international experts met in December 2008 at the First International Conference on Inflammatory Breast Cancer to develop guidelines for the management of IBC.
RESULTS: The panel of leading IBC experts formed a consensus on the minimum requirements to accurately diagnose IBC, supported by pathological confirmation. In addition, the panel emphasized a multimodality approach of systemic chemotherapy, surgery, and radiation therapy.
CONCLUSIONS: The goal of these guidelines, based on an expert consensus after careful review of published data, is to help the clinical diagnosis of this rare disease and to standardize management of IBC among treating physicians in both the academic and community settings.
Vered Stearns, C Alexander Ewing, Rebecca Slack, Marie F Penannen, Daniel F Hayes, Theodore N Tsangaris
Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer.
Ann Surg Oncol. 2002 Apr;9(3):235-42.
Abstract/Text
BACKGROUND: After neoadjuvant chemotherapy, women with locally advanced breast cancer (LABC) undergo a modified radical mastectomy or lumpectomy with axillary lymph node dissection (ALND) and radiotherapy. Sentinel lymphadenectomy (SL) is accepted for axillary evaluation in early breast cancer. We assessed the feasibility and predictive value of SL after neoadjuvant chemotherapy.
METHODS: Eligible women received neoadjuvant therapy for LABC and were scheduled to undergo a definitive surgical procedure. Vital blue dye SL was attempted followed by level I and II axillary dissection.
RESULTS: SL was successful in 29 of 34 patients (detection rate, 85%). Thirteen patients (45%) had positive nodes, and eight (28%) had negative nodes on both SL and ALND. In five patients (17%), the sentinel node was the only positive node identified. Overall, there was a 90% concordance between SL and ALND. The false-negative rate and negative predictive value were 14% and 73%, respectively. Among the subgroup without inflammatory cancer, the detection and concordance rates were 89% and 96%, respectively. The false-negative rate was 6%, and the negative predictive value was 88%.
CONCLUSIONS: SL after neoadjuvant chemotherapy may reliably predict axillary staging except in inflammatory breast cancer. Further studies are required to assess the utility of SL as the only mode of axillary evaluation in these women.
Corinne Veyret, Christelle Levy, Philippe Chollet, Yacine Merrouche, Henri Roche, Pierre Kerbrat, Pierre Fumoleau, Pierre Fargeot, Pierre Clavere, Bernard Chevallier
Inflammatory breast cancer outcome with epirubicin-based induction and maintenance chemotherapy: ten-year results from the French Adjuvant Study Group GETIS 02 Trial.
Cancer. 2006 Dec 1;107(11):2535-44. doi: 10.1002/cncr.22227.
Abstract/Text
BACKGROUND: The authors evaluated the long-term efficacy and side effects in patients with nonmetastatic, unilateral, inflammatory breast cancer (IBC) who received homogeneous treatment with intensive induction chemotherapy followed by a maintenance regimen.
METHODS: One hundred twenty patients were randomized to receive high-dose fluorouracil, epirubicin, and cyclophosphamide (FEC-HD) (fluorouracil 750 mg/m(2) on Days 1 to 4, epirubicin 35 mg/m(2) on Days 2 to 4, and cyclophosphamide 400 mg/m(2) on Days 2 to 4 for 4 cycles every 21 days) with or without lenograstim. Locoregional treatment consisted of surgery and/or radiotherapy. Maintenance chemotherapy was FEC 75 (fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) on Day 1 every 21 days for 4 cycles). No hormone treatment was allowed.
RESULTS: The safety of the FEC-HD regimen was described previously. Among 102 patients who underwent surgery, a pathologic complete response (pCR) was achieved by 23.5% of patients with breast tumors and by 31.4% of patients with involved axillary lymph nodes. The overall pCR rate was 14.7%. One hundred nine patients received FEC 75. After a median 10 years of follow-up, the disease-free survival (DFS) and overall survival (OS) rates were 35.7% and 41.2%, respectively. The median DFS was 39 months (95% confidence interval [95% CI], 25-53 months), and the median survival was 61 months (95% CI, 43-79 months). Five patients developed a temporary decrease in left ventricular ejection fraction without congestive heart failure. In the lenograstim group, 1 patient developed acute myeloblastic leukemia M2, and 1 patient developed myelodysplastic syndrome.
CONCLUSIONS: FEC-HD induction chemotherapy followed by FEC 75 maintenance regimen had moderate and acute long-term toxicities and lead to high DFS and OS rates in patients with IBC.
(c) 2006 American Cancer Society.
Luca Gianni, Wolfgang Eiermann, Vladimir Semiglazov, Alexey Manikhas, Ana Lluch, Sergey Tjulandin, Milvia Zambetti, Federico Vazquez, Mikhail Byakhow, Mikhail Lichinitser, Miguel Angel Climent, Eva Ciruelos, Belén Ojeda, Mauro Mansutti, Alla Bozhok, Roberta Baronio, Andrea Feyereislova, Claire Barton, Pinuccia Valagussa, Jose Baselga
Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort.
Lancet. 2010 Jan 30;375(9712):377-84. doi: 10.1016/S0140-6736(09)61964-4.
Abstract/Text
BACKGROUND: The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab.
METHODS: We compared 1 year of treatment with trastuzumab (given as neoadjuvant and adjuvant treatment; n=117) with no trastuzumab (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. Randomisation was done with a computer program and minimisation technique, taking account of geographical area, disease stage, and hormone receptor status. Investigators were informed of treatment allocation. A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen. Primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered, number ISRCTN86043495.
FINDINGS: Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% [95% CI 61-78; n=36 events] with trastuzumab, vs 56% [46-65; n=51 events] without; hazard ratio 0.59 [95% CI 0.38-0.90]; p=0.013). Trastuzumab was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs.
INTERPRETATION: The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival, survival, and clinical and pathological tumour responses.
FUNDING: F Hoffmann-La Roche.
Copyright 2010 Elsevier Ltd. All rights reserved.
Hamouda Boussen, Hatem Bouzaiene, Jamel Ben Hassouna, Tarek Dhiab, Fathi Khomsi, Farouk Benna, Amor Gamoudi, Nejib Mourali, Monia Hechiche, Khaled Rahal, Paul H Levine
Inflammatory breast cancer in Tunisia: epidemiological and clinical trends.
Cancer. 2010 Jun 1;116(11 Suppl):2730-5. doi: 10.1002/cncr.25175.
Abstract/Text
Inflammatory breast cancer (IBC) is characterized by a peculiar geographic distribution in incidence, being described as more common in Tunisia and the region of North Africa. The authors performed a systematic review of published literature on rapidly progressing breast cancer and IBC in Tunisia and analyzed the evolution in epidemiology, clinical presentation, treatment, and therapeutic results. They collected, analyzed, and compared all the indexed Tunisian articles about rapidly progressing breast cancer and IBC since the 1970s opening of the Institut Salah Azaiz Institute in Tunis. In the 1970s, rapidly progressing breast cancer diagnosis was based on the Poussée Evolutive classification (1-3). Since the 1990s, IBC diagnosis has been based on the American Joint Committee on Cancer Poussée Evolutive 3/T4d staging. The authors compared the historical data to the most recent publications in terms of epidemiology, clinical features, treatment, and therapeutic results. The most important historical report of rapidly progressing breast cancer concerned 340 patients, representing 58.5% of a cohort of 581 breast cancer patients collected from 1969 to 1974, including 320 (55.2%) with inflammatory signs, 37(6.5%) with Poussée Evolutive 2, and 283 (48.7%) with Poussée Evolutive 3. Subsequent papers have documented a steady decrease in incidence to the current 5% to 7% T4d/IBC. Since the 1970s, Poussée Evolutive in premenopausal woman has increased from 52.5% to 75%; rural predominance has persisted. The 5-year overall survival reached 28% by the year 2000. The authors' analysis demonstrated a trend of decreasing incidence of IBC diagnoses from 50% to presently <10%, probably related to a combination of factors, including the use of more stringent criteria (Poussée Evolutive 3/T4d) for IBC diagnosis and an improvement in the socioeconomic level of Tunisia.
Copyright 2010 American Cancer Society.
Hideko Yamauchi, Massimo Cristofanilli, Seigo Nakamura, Gabriel N Hortobagyi, Naoto T Ueno
Molecular targets for treatment of inflammatory breast cancer.
Nat Rev Clin Oncol. 2009 Jul;6(7):387-94. doi: 10.1038/nrclinonc.2009.73. Epub 2009 May 26.
Abstract/Text
Despite progress in combined-modality treatment with chemotherapy, surgery, and radiation therapy, the long-term outcome for patients with inflammatory breast cancer (IBC) remains poor. Therapies that target vasculolymphatic processes--angiogenesis, lymphangiogenesis, and vasculogenesis--have shown potential in the treatment for IBC, as represented by bevacizumab. Although the therapeutic effect of targeting lymphangiogenesis and vasculogenesis requires further investigation, targeting of angiogenesis has potential, not only through true antiangiogenic effects, but also through antitumor effects in concert with other pathways. Therapies that target cell proliferation pathways are the most promising targeted therapies for IBC. In particular, therapies that target human epidermal growth factor receptor 2 (for example, trastuzumab and lapatinib) have performed well in the clinical setting, leading to improved outcomes for patients with IBC. Metastatic pathways could have a unique, key role in the aggressiveness of the IBC phenotype. Further extensive work on the unique molecular characteristics of IBC is essential to ensure improved outcomes for patients with this disease. In this Review we discuss three pathways--vasculolymphatic, cell proliferation and metastatic--that could represent important targets in the treatment of IBC.
