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Indian Journal of Cancer, Vol. 47, No. 2, April-June, 2010, pp. 95-97 Guest Editorial Breast cancer: Search for new targets and improvement of existing techniques Bharath R, Parikh PM1 Assistant Professor and Medical Oncologist, PSG Institute of Medical Science and Research, Avinashi road, Peelamedu, Coimatore - 641 004, 1 Honorary Medical Oncologist, Hematologist and Convener, ICON ARO, Mumbai, India Correspondence Address: Dr. Bharath R, Assistant Professor and Medical Oncologist, PSG Institute of Medical Science and Research, Avinashi road, Peelamedu, Coimatore - 641 004, India bharath37@gmail.com Code Number: cn10030 PMID: 20448369 DOI: 10.4103/0019-509X.62993 Hereditary breast cancer syndromes, though uncommon, provide us with insights into the pathogenesis of these tumors. Women diagnosed with high risk breast cancer may avail of risk reduction strategies like bilateral mastectomy, bilateral salpingo-oophorectomy or chemoprevention in addition to close follow-up and screening to facilitate early detection. [1] The use of chemoprevention with Tamoxifen (for five years) is associated with a risk reduction of 40-50% but used uncommonly. [2] The logical direction of future research is therefore to identify targets in each specific high risk breast cancer genotype and tailor more effective therapy accordingly. Effective and targeted chemo preventive agents have the potential to treat such women who carry these mutations (breast cancer gene - BRCA- 1) without the need for physically and psychologically mutilating surgeries. In addition, down regulation of BRCA gene is noted in many sporadic breast cancers in the absence of mutations suggesting a link between this gene and breast cancer pathogenesis. Hockings et al. have proposed that activation of BRCA-1 transcription by estrogen requires occupancy of the BRCA-1 promoter by the unliganded aromatic hydrocarbon receptor. They have stressed the importance of the aromatic hydrocarbon ligands [benzo(a)pyrene [B(a)P] and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)] in activation of BRCA-1 promoter by estrogen. [3] In this issue, Wiwanitkit [4] explores the ligand binding sites on the BRCA-1 molecule using standard bioinformatics tools. The actual benefits of how such identification of ligands on the BRCA-1 molecule can influence treatment needs more laboratory and clinical work (e.g. identification of targets and molecules that bind to these targets and demonstration of efficacy as chemoprevention strategies in BRCA-1 mutation positive women or therapeutic targeting in sporadic breast cancers with down-regulated BRCA 1 gene [5] ). Wiwanitkit′s work, hopefully, will be an important step towards development of such targeted agents. The second article on breast cancer evaluates the quality of life (QoL) amongst younger women with the disease. [6] This study has looked at women less than 35 years of age, a special subgroup of very young women (most existing studies on younger patients included those less than 50 years of age). Younger women are expected to have a different psychological and body image perception compared to older women, a difference that can strongly influence the type of surgery opted for. [7],[8] In Indian women with breast cancer, quality of sexual life and sexual satisfaction are almost never discussed by the oncologists and patients - considered "taboo" topics. Numerous studies have shown that the overall QoL improves in breast cancer survivors with passage of time and this is confirmed in the present study. [9],[10],[11],[12] Hartl et al. in a similar long term follow-up study of QoL report better body image and sexual functioning in women who underwent BCS at the cost of increased fear of recurrence. [13],[14] Schover has looked at sexual function after breast cancer treatment and reported better body image perception in women after breast conservation. [15] Avis et al. have published results from two different studies specifically in younger women addressing QoL and sexual function. The body image perception and sexual function were worse in younger women with mastectomy. [15],[16],[17] The deterioration in sexual function was significantly higher in breast cancer survivors compared to non-patient women of similar age. This continued to increase as the women aged, with the breast cancer survivors requiring more intervention to aid sexual functioning. Janni et al. have reported results from a matched pair analysis in survivors of breast cancer comparing mastectomy with BCS and have found no difference in general QoL, but reported increased cosmetic dissatisfaction and consequent psychological stress. [18] The findings in the present study, among the very young breast cancer survivors, bring forth some important contradictions. They have reported non-improvement in body image score following BCS and increased fear of recurrence in the mastectomy group! This study emphasizes the fact that women younger than 35 years form a unique group; they are almost always premenopausal, lead more active professional and sexual life, need many years of follow-up to monitor recurrence and address treatment related long term toxicities. These very young women consequently require additional measures, beyond the standard QoL questionnaires, to identify their unique problems. [19],[20],[21] The article on breast cancer by Radhika and Prayaga in this issue is a comparison of immunocytochemistry (ICC) with immunohistochemistry (IHC) in evaluating hormonal receptor status in breast cancer. [22] Immunocytochemistry offers the pathologist an alternative technique to determine hormonal receptor status when tissue biopsy is unavailable or inadequate. The performance of ICC on destained papinocoloau slides has been a technique useful when adequate tissue is not available and a retrospective confirmation of malignancy is required. [23] This situation is commonly encountered in India where women with breast cancers receive neoadjuvant chemotherapy on the basis of a cytological diagnosis. Complete pathological response does occur in a significant fraction with consequent non-availability of viable cancer tissue for formal IHC. [23],[24] The changes in the hormonal receptor status induced by chemotherapy also need to be taken into consideration when IHC is being performed on post chemotherapy residual tissue submitted after mastectomy/BCS. The standardization of laboratory procedures including fixation, antigen retrieval and immunostaining has been a subject of intense work with a large number of publications in the last two decades. In spite of this, consensus is lacking across different laboratories. The shift of estrogen receptor (ER) testing by IHC on paraffin embedded tissue from the traditional Dextran coated charcoal assay (DCCA) has been an issue plagued by standardization issues and the further shift to ICC has been equally debated. [25],[26],[27] Gong et al. from M.D Anderson Cancer Center evaluated varying methods available for fixation of cytological smears (like Abbott method, 10% formalin at room temperature, Carnoy′s fixative followed by pap staining). Air drying of smears prior to fixation was also attempted in some smears. The importance of antigen retrieval in ER immunodetection has been emphasized in their paper. [28] Krishnamurthy et al. from the same group have demonstrated significant variability in ER immunocytochemical staining with different antibodies. [29] They also found poorer concordance in pap-destained smears as compared with pap stained smears for ER ICC performed using H222 monoclonal antibody in formaldehyde -methanol-acetone fixed smears. In contrast, the present article reports better ER ICC positivity with pap destained smears. [27] Since the authors have used both prospectively and retrospectively collected samples as well as different secondary antibodies, these differences may have had an impact on the results. The overall ER positivity rate reported by the authors is lower than that reported from the largest Indian series by Shet et al. Geographic variations, racial differences, selection bias (younger patients with higher stage and histological grade being referred to a large referral center) and technical issues may explain this variation. [30],[31] The significant differences in hormone receptor positivity with changes in fixation and antigen retrieval methods, antibodies used reported by Shet et al. compared to the previous study from the same center by Desai et al. should also prompt a closer look at all the steps involved. [32],[33],[34] The use of IHC in hormonal receptor testing is itself not standardized in many centers and the performance of ICC for hormone receptor testing should be taken up as routine practice only after rigorous standardization. The authors have demonstrated the feasibility of ICC, which is expected to be less expensive, compared to IHC and we must echo their words regarding the need of interlaboratory collaboration and external quality assurance schemes on national and international basis. This cannot be overemphasized considering that the hormonal receptor positivity and the methodology of determining hormone receptor status have both prognostic and therapeutic implications. References
Copyright 2010 - Indian Journal of Cancer |
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