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MINI SYMPOSIUM: BREAST- GUEST EDITORIAL
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Year : 2012  |  Volume : 49  |  Issue : 1  |  Page : 57--59

Locally advanced breast cancer: Prevention is better than cure!

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

Correspondence Address:
J Bajpai
Department of Medical Oncology, TATA Memorial Hospital, Mumbai
India




How to cite this article:
Bajpai J. Locally advanced breast cancer: Prevention is better than cure!.Indian J Cancer 2012;49:57-59


How to cite this URL:
Bajpai J. Locally advanced breast cancer: Prevention is better than cure!. Indian J Cancer [serial online] 2012 [cited 2022 May 20 ];49:57-59
Available from: https://www.indianjcancer.com/text.asp?2012/49/1/57/98920


Full Text

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!

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