FISH and HER2/neu equivocal immunohistochemistry in breast carcinoma.

AIM: The aim of this study was to validate the role of fluorescence in situ hybridization (FISH) in investigating HER2/neu gene amplification (human epidermal growth factor receptor 2) in patients with HER2/neu equivocal breast cancer diagnosed on immunohistochemistry (IHC). MATERIALS AND METHODS: This was a retrospective study conducted from January 2013 to October 2017. A total of 134 patients diagnosed with invasive breast carcinoma and HER2/neu equivocal status on IHC were analyzed. Also, the cases for the years 2016 and 2017 formed a subgroup that was analyzed further to study the impact of pre-analytical factors on IHC and FISH results. RESULTS: A total of 134 women with HER2/neu IHC equivocal breast cancer were included in the study with a median age of 50 years (range 25-81). HER2/neu amplification by FISH was noted in 72 (54%) cases, whereas it was non-amplified in 52 (39%) cases. Ten cases were reported as equivocal even on FISH (ASCO/CAP 2013 guidelines). Polysomy 17 was noted in 55 cases (41%), of which 26 patients were≤50 years and 29 patients were >50 years of age. Twenty (36%) of these 55 cases showed HER2/neu amplification, whereas 26 (48%) cases were non-amplified and 9 (16%) cases were reported as equivocal on FISH. Also, more than half of the polysomy cases were hormone receptor negative. CONCLUSION: IHC is a good screening tool for negative and positive results. Any patient targeted for trastuzumab therapy should undergo confirmation of HER2/neu equivocal status by FISH analysis. We also suggest that if a non-classical FISH pattern is seen, the test should be repeated with a non-centromeric chromosome 17 reference locus probe for better treatment planning.

Estrogen receptor, Progesterone receptor, and human epidermal growth factor receptor-2 status in breast cancer: A retrospective study of 5436 women from a regional cancer center in South India.

AIM: The aim of the study was to analyze the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status over 7 years in South Indian women with breast cancer. Further analysis of a subgroup was done to study clinically defined subtypes and the role of preanalytical factors in needle core biopsies (NCBs) and excised specimens. MATERIALS AND METHODS: This was a retrospective study from January 2010 to December 2016. Patients diagnosed with invasive breast cancer and available immunohistochemistry (IHC) reports of ER, PR, and HER2 status were analyzed. The cases for the year 2016 were analyzed further to observe the impact of preanalytical factors on the IHC staining patterns and surrogate status. RESULTS: A total of 5436 patients were included with a median age of 48 years. Among these, 65% were ≤ 55 years. The overall incidence of hormone receptor (HR)-positive patients was 48%; HER2 positive, 15%; and triple-negative breast cancer (TNBC), 37%. The incidence of HR positive, HER2 positive, and TNBC were 45%, 16%, and 39% and 53%, 13%, and 34% in patients <56 years and over 55 years, respectively (P < 0.001). There was an increase in HR positivity and decrease in TNBCs over time. There was no significant difference in the staining patterns in NCBs and excised specimens. CONCLUSION: With time, there is an increase in hormone-positive tumors which may be attributed to better IHC techniques and tissue handling. There was no statistical difference in the patterns of ER, PR, and HER2 immunostaining in core biopsy and excised specimens.

Clinical profile and treatment outcomes of metastatic neuroendocrine carcinoma: A single institution experience.

BACKGROUND: Neuroendocrine carcinoma (NEC) is a rare tumor arising from the diffuse neuroendocrine system. Most of these present in the advanced stage and palliative chemotherapy remains the only option. The prognosis remains poor with the standard chemotherapy regimen of platinum and etoposide (EP) providing modest survival benefit. METHODS: The study was done for 3 years at a tertiary cancer center in South India. Patients with a diagnosis of metastatic NEC were analyzed for clinical and pathological characteristics. The treatment outcomes and prognostic factors were evaluated using appropriate statistical test. RESULTS: A total of 114 patients of metastatic NEC satisfied the inclusion criteria and were analyzed. Gastrointestinal including hepatobiliary tract (33%) was the most common site of primary disease followed by lung (26%), genitourinary (15%), head and neck (14%), and unknown primary (9%). On analysis of pattern of metastasis, liver (65%) was the most common site followed by bone (54%) and lung (42%). The median overall survival was 11 months with a statistically significant difference between pulmonary and extrapulmonary disease (8 vs. 13 months; P = 0.003). Ki67% value was strongly associated with prognosis (hazard ratio 0.517, 95% confidence interval; 0.318-0.840, P = 0.008) whereas age, sex, and lactate dehydrogenase level did not show any relation with survival. CONCLUSION: The outcome of advanced NEC with standard chemotherapy remains poor. Larger studies with other therapeutic and novel agents are warranted to improve the treatment outcomes.

Correlation of BMI with breast cancer subtype and tumour size.

BACKGROUND: Breast cancer is a heterogeneous disease which is divided broadly into luminal, HER2 and basal type based on molecular profiling. Increased body mass index (BMI) has been associated with the risk of developing breast cancer but the association based on molecular subtype remains conflicting. METHODS: This was an observational study carried out over a period of 2 years. Nonmetastatic breast cancer patients were evaluated for the tumour subtype based on surrogate markers (ER, PR and HER2). The BMI of these patients was correlated with the tumour subtype and size. RESULTS: We studied 476 patients with breast cancer with the median age of 46 years (range, 25-86) and 58% were premenopausal. The mean BMI of the cohort was 24.1, which was significantly higher in postmenopausal women (24.9 versus 23.6, p < 0.05). Overall, only 10% of patients were obese. The mean BMI in the luminal, HER2 and TNBC subtypes was 24.7, 22.4 and 23.9, respectively (p < 0.01). Also, the mean tumour size in luminal, HER2 and TNBC subtype was 4.02, 3.80 and 4.27 cm, respectively (p = 0.158). CONCLUSION: The average BMI was higher in patients with luminal subtype followed by TNBC and lowest for HER2 at the time of diagnosis. The mean tumour size was numerically higher for TNBC and lowest for HER2 subtype although the difference was not statistically significant. Larger studies may provide clarity of association between the BMI and tumour subtype.