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Year : 2012  |  Volume : 49  |  Issue : 1  |  Page : 57-59

Locally advanced breast cancer: Prevention is better than cure!

Department of Medical Oncology, TATA Memorial Hospital, Mumbai, India

Date of Web Publication25-Jul-2012

Correspondence Address:
J Bajpai
Department of Medical Oncology, TATA Memorial Hospital, Mumbai
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-509X.98920

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How to cite this article:
Bajpai J. Locally advanced breast cancer: Prevention is better than cure!. Indian J Cancer 2012;49:57-9

How to cite this URL:
Bajpai J. Locally advanced breast cancer: Prevention is better than cure!. Indian J Cancer [serial online] 2012 [cited 2022 Jun 26];49:57-9. Available from:

Locally advanced breast cancer (LABC) represents some of the most aggressive breast cancers. Although in USA only 10-20% of all breast cancer patients present as LABC, in India, 30-60% present as a LABC. [1] LABC was initially commonly defined as breast cancers that were inoperable at presentation and/or as having an extremely poor survival with locoregional treatments alone. [1] However, now LABC refers to large breast tumors (>5 cm) associated with either the skin or chest wall involvement or with fixed axillary lymph nodes or disease spread to ipsilateral internal mammary node or supraclavicular node. [2]

The article that accompanies this editorial by Akhtar et al. presents a challenge and a model to evaluate the prevalence of LABC and for assessing the causes of local advancement and delayed presentation of the breast cancer in developing world. In this rural hospital-based prospective study conducted in 71 breast carcinoma cases, the author demonstrated the prevalence of LABC and causes of delay and local advancement. On assessment, patient factor (69.8%) was the major cause for delayed presentation, followed by system delay (23.6%). Patient factors were lack of awareness of breast cancer (75%) and financial constraints (52.8%); the system factor was nonreferral by general practitioners to specialty centers or trying to treat these patients with other allied modalities of treatment. One may conclude that LABC in the underdeveloped/developing world is an outcome of constant neglect due to patient and system factors. Author enlightens us about these factors and this might be an excellent opportunity to plan a community-oriented preventive strategy to decrease the incidence of LABC in this part of the world by merely educating people and their general practitioners.

Further, the common thread regarding LABC is the consideration of neoadjuvant systemic therapy (NST) as the initial management of choice. The intent of NST specifically in the LABC cohorts includes earlier treatment of subclinical distant micrometastases, downstaging of the primary tumor, which may then allow for operability (including breast-conservation surgery in some instances), and the ability for an in vivo assessment of response to specific systemic agents. The magnitude of benefit from NST on survival, however, is unclear as a result of the few comparative trials specifically in LABC. Given the results of the neoadjuvant versus adjuvant chemotherapy trials in primary operable breast cancer demonstrating equivalent outcomes, [3],[4] and the advantages of NST as outlined above, it is not only rational but also current practice to apply this approach in inoperable LABC. The few randomized trials in stage III breast cancer that first used local therapy followed by systemic therapy or only local therapy have shown a survival advantage for the combined-modality approach. [5],[6],[7],[8] The 2000 Early Breast Cancer Trialist' Collaborative Group overview of polychemotherapy in breast cancer demonstrated that anthracycline-based regimens were superior to nonanthracycline-based therapies, with improved disease-free survival (DFS) and overall survival (OS). [9],[10] The next generation of randomized clinical trials evaluated paclitaxel and docetaxel. These agents were well established in the treatment of metastatic breast cancer and lacked cross-resistance with the anthracyclines, which supported their evaluation in the adjuvant setting. [11] Using these studies, a meta-analysis showed that the addition of a taxane to an anthracycline-based regimen improved DFS and OS in high-risk patients regardless of age, menopausal status, the number of nodes involved, hormone receptor status, and the type of taxane. [12]

In the other article that also accompanies this editorial, the author reported the results of the retrospective single institutional study conducted to compare taxane-based and anthracycline-based NST. During the 8-year period (2000-2007), out of a total of 3000 breast cancer cases, 570 (19%) were LABC and 91 [37 docetaxel (D)], 54 anthracycline (A)] patients were eligible for response and survival analysis. Pathological complete remission (pCR) was defined as no evidence of malignancy in both breast and axilla. Overall clinical response rates (ORR) for breast primary were 74.3% and 53.7% (CR 28.6% vs. 16.7%, P = 0.58), while for axilla the ORR were 75.7% and 54.8% (CR 51.4% vs. 40.4%, P = 0.77), respectively, for D and A. The corresponding pCR rates were 19% and 13%, respectively. There was no significant difference in DFS (3-year DFS 56.84% vs. 61.16%, P = 0.80) and OS (3-year OS 70% vs. 78.5%, P = 0.86) between the two groups. Authors concluded that although pCR rates were higher with docetaxel-based NST, it did not translate into superior DFS/OS compared to anthracycline-based NST.

The pathological complete response (pCR) has been shown to be an independent predictor of prolonged DFS/OS, but very few patients achieve pCR and that too is dependent upon the type of chemotherapy. [13] Earlier trials testing anthracyclines as NST produced pCR rates of 2-13% and there was no difference in DFS/OS. [14],[15],[16],[17] Subsequently, taxanes have been used either alone or with anthracyclines and they have shown to improve pCR rates. Single agent docetaxel has produced pCR rates of 16-20% and clinical complete responses (cCR) from 18% to >25%. [18],[19],[20],[21] In combination with anthracyclines, pCR rates from 10% to >20% are reported depending upon the stages of tumor included in that particular study. [22],[23],[24],[25],[26],[27] The pCR and cCR in this study are comparable to the results previously reported in the literature. Historically, NST has not led to increased DFS/OS, but achieving pCR is associated with longer DFS/OS. In a recent update of National Surgical Adjuvant Breast and Bowel Project NSABP B-18 and B-27 trials, there was no survival advantage with NST and addition of taxane to NST did not translate into higher survivals although pCR rates were higher. [15],[28]

While this study is interesting and hypothesis generating, the strength of the findings is limited by several factors. Being retrospective in nature, there is disparity in the number of patients, number of cycles administered before surgery and even in the median follow-up of the two groups. Further, in the current era, hormone receptors and Her-2 expression of the tumor clone carry an important bearing both in therapeutic and prognostic implications and cannot be ignored; especially in Her-2-positive cancers, specific targeted therapy improves the outcome many folds. Although the authors concluded that in spite of the pCR rates being higher with docetaxel-based NST, it did not translate into superior DFS/OS compared to anthracycline-based NST, and hence both regimens are equal in efficacy and represent appropriate treatment options. For clinicians, it is reasonable to ask how this should influence practice when the literature evidence exists for as well as against that pCR is an important surrogate for survival.

Comparable different regimens with the different toxicity profiles allow us to make more informed treatment recommendations in the clinic. With this accomplished, we should ask what our next steps should be. Are similar head-to-head comparisons of effective chemotherapy regimens the best use of our limited resources? Should our focus be switched to develop more effective and less toxic options rather than be on massive chemotherapy trials and novel therapies? At the same time, we must acknowledge the practical reality that our patients in clinic today need effective taxane- and/or anthracycline-based regimens and appropriate judgment is warranted in each individual case. The author reminds us that we have options even as we strive for better ones.

To summarize, both the articles focus a spotlight on our need to increase the level of cancer awareness of our population/general practitioners and then to rationalize an otherwise uninterpretable menu of options for the treatment, especially in LABC. A successful effort at making headway in this regard will require the sort of collaborative spirit that was modeled by this group of investigators to share their data and resources in a way that accelerates knowledge regarding factors associated with constant neglect of the disease presence. Patients with LABC should be encouraged to participate in clinical trials to further define the best management options. Going forward, such efforts will be bound to include the knowledge of best use of the limited diagnostic and therapeutic options available in a resource-constrained setting, not simply as a snapshot of a fixed and final state, but as the dynamic entities we so often observe them to be. Last but not the least, the old dictum holds true for LABC, "prevention is always better than cure" and must be remembered!

 » References Top

1.Valero VV, Buzdar AU, Hortobagyi GN. Locally advanced breast cancer. Oncologist 1996; 1:8-17.   Back to cited text no. 1
2.Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, et al. Revision of American Joint Committee on Cancer Staging System for Breast Cancer. J Clin Oncol 2002; 20:3628-36.  Back to cited text no. 2
3.Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 1998;16:2672-85.  Back to cited text no. 3
4.Van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: Results from the European Organization for Research and Treatment of Cancer Trial 10902. J Clin Oncol 2001;19:4224-37.   Back to cited text no. 4
5.Caceres B, Zaharia M, Lingan M, Valdivia, S., Moran, M. Tejada et al. Combined therapy of stage III adenocarcinoma of the breast. Proc Am Assoc Cancer Res 1980; 21:199.  Back to cited text no. 5
6.Knight WA 3rd, Rivkin SE, Glucksberg H, Foulkes MA, Costanzi JJ, Stephens RL, et al. Adjuvant therapy of breast cancer: The Southwest Oncology Group experience. Breast Cancer Res Treat 1983;3 Suppl:S27-33.  Back to cited text no. 6
7.Buzdar AU, Kau SW, Smith TL, Hortobagyi GN. Ten year results of FAC adjuvant chemotherapy trial in breast cancer. Am J Clin Oncol 1989;12:123-8.  Back to cited text no. 7
8.Bartelink H, Rubens RD, van der Schueren E, Sylvester R. Hormonal therapy prolongs survival in irradiated locally advanced breast cancer: A European Organization for Research and Treatment of cancer randomized phase III trial. J Clin Oncol 1997;15:207-15.  Back to cited text no. 8
9.Early Breast Cancer Trialists' Collaborative Group (EBCTCG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 2005;365:1687-717.  Back to cited text no. 9
10.Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Clarke M, Coates AS, Darby SC, Davies C, Gelber RD, et al. Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: Patient-level meta-analysis of randomised trials. Lancet 2008;371:29-40.  Back to cited text no. 10
11.Crown J, O'Leary M, Ooi WS. Docetaxel and paclitaxel in the treatment of breast cancer: A review of clinical experience. Oncologist 2004;9:24-32.  Back to cited text no. 11
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13.Machiavelli MR, Romero AO, Perez JE, Lacava JA, Dominguez ME, Rodriguez R, et al. Prognostic significance of pathological response of primary tumor and metastatic axillary lymphnodes after neoadjuvant chemotherapy for locally advanced breast carcinoma. Cancer J Sci Am 1998;4:125-31.   Back to cited text no. 13
14.Raina V, Medhi K, Deo S, Shukla NK, Mohanti BK, Rath GK. Outcome of combined modality treatment of 412 cases of locally advanced breast cancer (LABC): Data from a tertiary cancer center in India. Breast Cancer Res Treat 2007;106 Suppl 1:S1-350.  Back to cited text no. 14
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16.Deo SV, Bhutani M, Shukla NK, Raina V, Rath GK, Purkayasth J. Randomized trial comparing neoadjuvant vs adjuvant chemotherapy in locally advanced breast cancer (T4bN0-2M0). J Surg Oncol 2003;84:192-7.   Back to cited text no. 16
17.vander Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: Results from the European Organization for Reasearch and Treatment of Cancer trial 10902. J Clin Oncol 2001;19:4224-37.   Back to cited text no. 17
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19.Amat S, Bougnoux P, Penault-Lorca F, Fetissof F, Cure H, Kwiatkowski F, et al. Neoadjuvant Docetaxel for operable breast cancer induces a high pathological response and breast conservation rate. Br J Cancer 2003;88:1339-45.   Back to cited text no. 19
20.Estevez LG, Cuevas JM, Anton A, Florian J, Lopez-Vega JM, Velasco A, et al. Weekly Docetaxel is effective as neoadjuvant chemotherapy for stage II and stage III breast cancer. Efficacy and correlation with biological markers in a phase II, multicenter study. Clin Cancer Res 2003;9:686-92.   Back to cited text no. 20
21.Tham YL, Gomez LF, Mohsin S, Gutierrez MC, Weiss H, Hilsenbeck SG, et al. Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers. Breast Cancer Res Treat 2005;94:279-84.   Back to cited text no. 21
22.De Matties A, Nuzzo F, D'Aiuto G, Labonia V, Landi G, Rossi E, et al. Docetaxel plus Epirubicin as neoadjuvant treatment in patients with large operable or locally advanced braest cancer. Cancer 2002;94:895-901.   Back to cited text no. 22
23.Valero V, Esteva FJ, Sahin AA. Phase II trial of neoadjuvant chemotherapy with doctaxel and doxorubicin, surgery, adjuvant CMF, and radiotherapy +/- tamoxifen in locally advanced breast cancer. Breast Cancer Res Treat 2000;64:9.   Back to cited text no. 23
24.von Minckwitz G, Costa SD, Eiermann W, Blohmer JU, Tulusan AH, Jackisch C, et al. Maximized reduction of primary breast tumor size using preoperative chemotherapy with doxorubicin and Docetaxel. J Clin Oncol 1999;17:1999-2005.   Back to cited text no. 24
25.Espinosa E, Morales S, Borrega P, Casas A, Madronal C, Machengs I, et al. Docetaxel and high dose Epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer. Cancer Chemother Pharmacol 2004;54:546-52.   Back to cited text no. 25
26.Baltali E, Altundag MK, Onat DA, Abbasoglu O, Ozisik Y, Guler N, et al. Neoadjuvant chemotherapy with Taxotere-epirubicin-5-fluorouracil (TEF) in loco regionally advanced breast cancer: A preliminary report. Tumori 2002;88:474-7.   Back to cited text no. 26
27.Hirano A, Shimizu T, Imamura H, Watanabe O, Kinoshita J, Okabe T, et al. The combination of epirubicin plus Docetaxel as neoadjuvant chemotherapy in locally-advanced breast cancer. Anticancer Res 2006;26:581-4.   Back to cited text no. 27
28.Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, et al. The effect on tumor response of adding preoperative Docetaxel to preoperative Doxorubicin and Cyclophosphamide: Prelimnary results from National Surgical Adjuvant Breast and Bowel Project protocol B-27. J Clin Oncol 2003;21:4165-74.  Back to cited text no. 28

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