To the Editor:
The meta-analysis of breast cancer demographics in Indian patients by Sandhu et al1 highlights significant variability in estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) status and presenting age reported by various authors and then pools the data to ascertain the rate of triple-negative breast cancer (TNBC) to be around 31%. We feel that such a report may overlook a few important issues, which we would like to outline. The authors rightly highlight that local, environmental, and physical factors may contribute to the heterogeneity but have not explored some of them. Of the studies included, only four centers reported an average of over 20 patients per month. Small series, such as that by Akhtar et al,2 are likely to be unrepresentative of the regional population and could present a selection bias. However, the referral patterns for high-volume tertiary care centers may also contribute significantly to the selection bias, which is reflected in the younger age in some of these series. In addition, some studies, such as those by Nandi et al3 and Ambroise4 et al, reported immunohistochemistry (IHC) only on patients receiving curative therapy, in contrast to others, who reported on all patients who presented to the hospital. This could also contribute to the heterogeneity reported.
Some technical issues also need to be highlighted. The majority of these studies have used manual methods to determine IHC status, whereas automated methods using adequately fixed and processed tissue standardizes the technique with fewer testing variations compared with manual methods.5 In addition, many of the studies did not report the antibodies used or whether they followed optimal preanalytic requirements, such as cold ischemia time and adequate fixation. In most of the studies included in the analysis, IHC was performed on lumpectomies or mastectomies rather than on core biopsies; this itself may lead to a 9% false-negative ER result.6 Core biopsies are better specimens because of less cold ischemia time and quick formalin infiltration, resulting in uniform and consistent fixation.7 In addition, with the advent of robust rabbit monoclonal antibodies with improved sensitivity and specificity, such as SP1 for ER and 1E2 for PR, low levels of ER and PR are being detected, possibly reducing the number of triple-negative patients.8
We recently published the IHC status of unselected patients receiving curative therapy in a tertiary care center in eastern India between June 2011 and December 2013.9 Our overall rates of TNBC were 12.5%, with 15.5% for those with locally advanced tumors. Following the meta-analysis by Sandhu et al,1 we looked at our more recent data for 2014 and 2015, which showed persistent TNBC rates of 11.9% and 11.3%, respectively, with a further 5.1% and 4.4% for ER-negative/PR-negative HER2 2+ disease, where fluorescent in situ hybridization evaluation of HER2 positivity was not available. For all patients in our series, IHC was tested on mostly core biopsies using automated, approved, and peer-reviewed methods, with appropriate internal and formal external quality assurance.
The heterogeneity in the reported prevalence of TNBC and, in general, the prevalence of various luminal tumor types are likely to be multifactorial as mentioned previously. A pooled meta-analysis with the Indian-patient tag may be simplistic and may not be the actual representation, which a prospective population-based study of breast cancer with appropriate quality assurance will provide.
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc.
Sanjoy Chatterjee
No relationship to disclose
Indu Arun
No relationship to disclose
Sanjit Agrawal
No relationship to disclose
Moses Arunsingh
No relationship to disclose
Indranil Mallick
Employment: Mylan (I)
Rosina Ahmed
No relationship to disclose
REFERENCES
- 1. Sandhu GS, Erqou S, Patterson H, et al: Prevalence of triple-negative breast cancer in India: Systematic review and meta-analysis. J Glob Oncol 2:412-421, 2016. [DOI] [PMC free article] [PubMed]
- 2.Akhtar M, Dasgupta S, Rangwala M. Triple negative breast cancer: An Indian perspective. Breast Cancer (Dove Med Press) 2015;7:239–243. doi: 10.2147/BCTT.S85442. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Nandi M, Mahata A, Mallick I, et al. Hypofractionated radiotherapy for breast cancers--preliminary results from a tertiary care center in eastern India. Asian Pac J Cancer Prev. 2014;15:2505–2510. doi: 10.7314/apjcp.2014.15.6.2505. [DOI] [PubMed] [Google Scholar]
- 4.Ambroise M, Ghosh M, Mallikarjuna VS, et al. Immunohistochemical profile of breast cancer patients at a tertiary care hospital in South India. Asian Pac J Cancer Prev. 2011;12:625–629. [PubMed] [Google Scholar]
- 5.Prichard JW. Overview of automated immunohistochemistry. Arch Pathol Lab Med. 2014;138:1578–1582. doi: 10.5858/arpa.2014-0083-RA. [DOI] [PubMed] [Google Scholar]
- 6.Gown AM. Current issues in ER and HER2 testing by IHC in breast cancer. Mod Pathol. 2008;21(suppl 2):S8–S15. doi: 10.1038/modpathol.2008.34. [DOI] [PubMed] [Google Scholar]
- 7.Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31:3997–4013. doi: 10.1200/JCO.2013.50.9984. [DOI] [PubMed] [Google Scholar]
- 8.Cheang MC, Treaba DO, Speers CH, et al. Immunohistochemical detection using the new rabbit monoclonal antibody SP1 of estrogen receptor in breast cancer is superior to mouse monoclonal antibody 1D5 in predicting survival. J Clin Oncol. 2006;24:5637–5644. doi: 10.1200/JCO.2005.05.4155. [DOI] [PubMed] [Google Scholar]
- 9. doi: 10.1016/j.clon.2016.05.008. Chatterjee S, Arunsingh M, Agrawal S, et al: Outcomes following a moderately hypofractionated adjuvant radiation (START B type) schedule for breast cancer in an unscreened non-Caucasian population. Clin Oncol (R Coll Radiol) 10.1016/j.clon.2016.05.008 [epub ahead of print on June 28, 2016] [DOI] [PubMed] [Google Scholar]