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Year : 2010  |  Volume : 47  |  Issue : 1  |  Page : 1--2

Breast cancer in India: A continuing challenge

S Gupta 
 Associate Professor of Medical Oncology and Convener, Breast Cancer Working Group, Tata Memorial Hospital, Mumbai - 400 012, India

Correspondence Address:
S Gupta
Breast Cancer Working Group, Tata Memorial Hospital, Mumbai - 400 012

How to cite this article:
Gupta S. Breast cancer in India: A continuing challenge.Indian J Cancer 2010;47:1-2

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Gupta S. Breast cancer in India: A continuing challenge. Indian J Cancer [serial online] 2010 [cited 2022 Aug 17 ];47:1-2
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ERBB2 is the official name provided by the HUGO Gene Nomenclature Committee for the v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 gene that encodes a member of the epidermal growth factor receptor family of receptor tyrosine kinases. It is also commonly referred to as HER2 and is an orphan receptor in the sense of having no known ligand. It is the preferred heterodimerization partner of its cousins when one of them is bound by a ligand. Its amplification and overexpression in human breast cancer has been correlated with poor prognosis. [1] Although somewhat controversial, it has also been reported to be predictive of relative resistance to endocrine therapies, especially selective estrogen receptor modulators, relative resistance to nonanthracycline nontaxane chemotherapy regimens and relative sensitivity to antracyclines and taxanes. However, its prognostic and predictive capabilities are not the main reasons for the excitement surrounding this receptor in the scientific literature and lay press.

Since its initial discovery in 1986, HER2 was intensively researched as a therapeutic target. The reports of the efficacy of trastuzumab, a recombinant humanized monoclonal antibody that binds with high affinity to HER2, in advanced breast cancer [2],[3] marked the culmination of that search. Since that time, the indications for its use have rapidly expanded. Its incorporation as a component of adjuvant therapy in HER2-positive tumors has been shown to significantly improve both disease-free and overall survival in a number of randomized trials. HER2 overexpression has been reported in 18-25% of breast cancers depending on the methodology used. A number of tests are in current use for the estimation of HER2 status, both at the protein and the genetic level. The two most commonly used tests are immunohistochemistry (IHC) and fluorescent in situ hybridization. There are a number of methodological issues in the appropriate standardization, performance and interpretation of all these tests-the results are discrepant in up to 20% cases when central testing in high-volume laboratories are compared with individual institutional results. [4],[5]

It is in the above background that one must contextualize the study by Vaidyanathan et al. on HER2-positive breast cancer, reported in this issue of the Journal. [6] The study evaluated the HER2 overexpression in Indian women with sporadic breast cancer and its correlation with other clinical and pathological variables. They studied the HER2 expression in a prospective cohort of 55 (presumably) unselected patients by genomic polymerase chain reaction (PCR) and IHC and by IHC in a retrospective group of 313 patients, whose paraffin blocks were available. Survival information was available in 179 of 368 patients. Noteworthy results from their study included a statistical association of HER2 expression with lymph node positivity, larger tumor size, ductal histology and relapse. However, the most interesting result from their study was the different rate of HER2 positivity by IHC (43.2%) and genomic PCR (25.5%). Although the authors state that other mechanisms of HER2 overexpression could be responsible, it is unlikely that this could account for the 17.7% overreporting by IHC. For example, polysomy 17 is a recognized mechanism of HER2 overexpression independent of gene amplification, but is found in [7] Moreover, it is unlikely that any group of unselected Indian patients will have such a high rate of HER2 expression, as indicated by the IHC results. The IHC results are also surprising in that of the 159 positive cases, 151 were 3+ and only eight were 2+. It is likely that the IHC results are due to methodological issues that have been highlighted in a well-collated guideline on this topic. [8] Survival information was available in et al. is a valuable addition to the existing literature on this topic from India and reaffirms the negative prognostic significance of a group of HER2-positive patients who did not have access to specific anti-HER2 therapies.

The second study on breast cancer by Sandhu et al.[9] in this issue of the Journal reports on the clinical, epidemiological and treatment characteristics of 304 patients presenting to the general surgical and surgical oncology units of a large referral hospital in the northern Indian state of Haryana. Like almost every other study from India, this study also reports an average age (47 years) that is almost 10 years lower than the West. This is the result of the age structure of the Indian population, which is a bottom-heavy (predominantly young) pyramid. In support of this fact, almost all common adult cancers have the highest age-specific incidence rates in the seventh or eighth decades of life in well-collected data from population-based cancer registries. Risk factor analysis for parity, age at menarche/menopause, rural/urban residence etc. is best performed in the context of either case-control or prospective cohort studies, and is difficult to interpret in a hospital series. Although shorter duration of symptoms could mean earlier presentation to the healthcare system, it could also indicate aggressive disease. This analysis would be more insightful if it is performed after controlling for stage. There are a number of interesting observations in this study. None of the 304 patients is reported to have a positive family history. Although this could indicate the low incidence of hereditary breast cancer in this population, it could also be the result of the retrospective nature of the study and the incompleteness of history taking and record keeping. As indicated in this study, there continues to be a marked preference for mastectomy over breast conservation in many parts of India-the logistics of delivering a relatively prolonged course of radiation being a primary impediment. The overwhelming majority (almost 90%) was from a lower socioeconomic background, although the criteria for this evaluation are not mentioned in the paper. Such patients present potential challenges in completion of multimodality treatment and retention to follow-up. More than half (54.6%) of all patients had stage III disease, indicating the extant late presentation of breast cancer in many parts of India. The greater use of neoadjuvant chemotherapy, anthracycline regimens and compliance to treatment in the surgical oncology patients (in contrast to those treated by general surgeons) emphasizes the need for specialized oncology departments in medical colleges.

The two breast cancer studies are a continuing reminder that India is indeed a land of many contrasts. The future challenge will be to harmonize the minimum standards of care across the country so that patients can be assured of optimum management wherever they present to the healthcare system.


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