A multi-institutional real world data study from India of 3453 non-metastatic breast cancer patients undergoing upfront surgery.

The present analysis reports the clinical, pathological, treatment profile and overall survival (OS) and disease-free survival (DFS) outcomes of consecutive breast cancer patients from three Indian centres, who underwent curative surgery as their first treatment. Among the 3453 patients, stage I, II, and III cases were 11.75%, 66.79%, and 21.64%, respectively while hormone receptor positive/HER2 negative, triple negative (TNBC) and hormone receptor any/HER2 positive cases were 55.2%, 24.2% and 20.6%, respectively. The five-year OS in the entire cohort, node-negative and node-positive patients were 94.1% (93.25-94.98), 96.17% (95.2-97.15) and 91.83% (90.36-93.31), respectively, and the corresponding DFS were 88.1% (86.96-89.31), 92.0% (90.64-93.39) and 83.93% (82.03-85.89), respectively. The five-year OS in hormone receptor positive/HER2 negative, TNBC and HER2 subgroups were 96.11% (95.12-97.1), 92.74% (90.73-94.8) and 90.62% (88.17-93.15), respectively, and the corresponding DFS were 91.59% (90.19-93.02), 85.46% (82.79-88.22) and 81.29% (78.11-84.61), respectively. This is the largest dataset of early breast cancer patients from India with survival outcome analysis and can therefore serve as a benchmark for future studies.

Treatment of elderly breast cancer patients in a breast center in India.

CONTEXT: The management of breast cancer in older patients is challenging due to factors such as comorbidities, limited mobility, functional dependence, cognitive functions, and socioeconomic aspects. Data about the outcomes in elderly patients with breast cancer in our country are sparse. AIMS: The aim of this study was to evaluate and compare the clinical and pathological variables, treatment, and survival outcomes of elderly women (those of 70 years and above) with women under 50 years and those between the ages of 50 and 69 years treated at our center. SUBJECTS AND METHODS: Prospectively collected clinical and pathological data from January 2007 to December 2014 were recorded and entered into OncoCollect™ software. Statistical analysis was done using Microsoft R Open software. Survival analysis was estimated using Kaplan-Meier curves. RESULTS: A total of 1226 Stage I-III breast cancer patients were treated between January 2007 and December 2014. Of these, 11.3% (139) were aged 70 years and above. Invasive ductal carcinoma was predominant and majority had Stage II disease and grade 1 tumors. Receptor positivity was observed in 79% of elderly patients and 9% had triple-negative disease. Primary hormone therapy was given to 7% of the patients and chemotherapy was administered to 12%. The 5-year overall survival for patients 70 years and older is 85%. CONCLUSIONS: Elderly patients are more likely to have an indolent course with low grade and estrogen receptor-positive tumors. For healthy older women, treatment according to standard guidelines including surgery, chemotherapy, and radiation should be followed. However, for those who are unfit and cannot tolerate surgery, primary endocrine therapy is a suitable option.

Role of magnetic resonance imaging in breast cancer management.

Magnetic resonance imaging (MRI) of the breast is primarily used as a supplemental tool to breast screening with mammography or ultrasound. A breast MRI is mainly used for women who have been diagnosed with breast cancer, to help measure the size of the cancer, look for other tumors in the breast, and to check for tumors in the opposite breast. For certain women at high risk for breast cancer, a screening MRI is recommended along with a yearly mammogram. MRI is known to give some false positive results which mean more test and/or biopsies for the patient. Thus, although breast MRI is useful for women at high risk, it is rarely recommended as a screening test for women at average risk of breast cancer. Also, breast MRI does not show calcium deposits, known as micro-calcifications which can be a sign of breast cancer.

Synchronous Bilateral Breast Cancers.

BACKGROUND: Bilateral breast cancer (BBC) is not an uncommon entity in contemporary breast clinics. Improved life expectancy after breast cancer treatment and routine use of contra-lateral breast mammography has led to increased incidence of BBC. Our study objective was to define the epidemiological and tumour characteristics of BBC in India. MATERIALS AND METHODS: A total of 1251 breast cancer patients were treated during the period January 2007 to March 2015 and 30 patients were found to have BBC who constituted the study population (60 tumour samples). Synchronous bilateral breast cancers (SBC) was defined as two tumours diagnosed within an interval of 6 months and a second cancer diagnosed after 6 months was labelled as metachronous breast cancer (MBC). Analyses of patient and tumour characteristics were done in this prospective data base of BBC patients. RESULTS: Median patient age was 66 years (range 39-85). Majority of the patients had SBC (n=28) and in 12 patients the second tumour was clinically occult and detected only by mammography of the contra-lateral breast. The second tumour was found at lower tumour size compared to the first in 73% of cases and was negative for axillary metastasis in 80% of cases (24/30). Infiltrating ductal carcinoma was the commonest histological type (n=51) and majority of the tumours were ER/PR positive (50/60). Her2 was overexpressed in 13 tumours (21%). Over 70% (22/30) of patients had similar histology in both breasts and amongst them grade concordance was present in about 69% (15/22) of patients. Concordance rates of ER, PR and Her2 statuses were 83%, 80% and 90% respectively. Bilateral mastectomy was the commonest surgery performed in 80% of the patients followed by bilateral breast conservation in 13%. At the end of study period, 26 patients were alive and disease free. Median survival was 29 months (range 3-86 months). CONCLUSION: In most patients with BBC, the second tumour is identified at an early stage than index tumours supporting the importance of contralateral breast cancer screening at the time of primary diagnosis and during follow-up. BBC occurs more frequently in old age group and majority of these tumours are estrogen dependent. There is good pathological concordance between the index tumour and the contralateral breast cancer.

Factors Influencing Non-sentinel Node Involvement in Sentinel Node Positive Patients and Validation of MSKCC Nomogram in Indian Breast Cancer Population.

Current guidelines recommend completion axillary lymphnode dissection (ALND) when sentinel lymphnode (SLN) contains metastatic tumor deposit. In consequent ALND sentinel node is the only node involved by tumor in 40-70 % of cases. Recent studies demonstrate the oncologic safety of omitting completion ALND in low risk patients. Several nomograms (MSKCC, Stanford, MD Anderson score, Tenon score) had been developed in predicting the likelihood of additional nodes metastatic involvement. We evaluated accuracy of MSKCC nomogram and other clinicopathologic variables associated with additional lymph node metastasis in our patients. A total of 334 patients with primary breast cancer patients underwent SLN biopsy during the period Jan 2007 to June 2014. Clinicopathologic variables were prospectively collected. Completion ALND was done in 64 patients who had tumor deposit in SLN. The discriminatory accuracy of nomogram was analyzed using Area under Receiver operating characteristic curve (ROC). SLN was the only node involved with tumor in 69 % (44/64) of our patients. Additional lymph node metastasis was seen in 31 % (20/64). On univariate analysis, extracapsular infiltration in sentinel node and multiple sentinel nodes positivity were significantly associated (p < 0.05) with additional lymph node metastasis in the axilla. Area under ROC curve for nomogram was 0.58 suggesting poor performance of the nomogram in predicting NSLN involvement. Sentinel nodes are the only nodes to be involved by tumor in 70 % of the patients. Our findings indicate that multiple sentinel node positivity and extra-capsular invasion in sentinel node significantly predicted the likelihood of additional nodal metastasis. MSKCC nomogram did not reliably predict the involvement of additional nodal metastasis in our study population.

Clinical response to primary letrozole therapy in elderly patients with early breast cancer: possible role for p53 as a biomarker.

Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70-101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI - 34-72) and the median time to progression was 43 months (95% CI - 22-64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group.

Needle core biopsy for breast lesions: An audit of 467 needle core biopsies.

BACKGROUND: Breast cancer is the commonest cancer among women in urban India. Triple assessment includes clinical, radiological and cytological assessment of breast lesions. Guided core needle biopsy has replaced fine needle aspiration cytology in most of the western countries. In resource poor countries FNAC is still a very valuable and cost effective method to diagnose breast lesions. Pitfalls include increased rates of non diagnostic smears, and inadequate smears. Further procedures may be required and this increases the cost, anxiety and delay in diagnosis. AIMS: The aim of this study is to analyze the concordance of radiological and histopathology findings in BI-RADS category 3,4,5 lesions following a core biopsy. MATERIALS AND METHODS: Data was retrospectively collected from consecutive symptomatic and opportunistic screen detected patients with abnormalities who underwent ultrasound guided interventional procedures from Jan 2010 to Aug 2011. Symptomatic patients underwent clinical examination, mammogram and breast ultrasound. Women under 35 years of age had only breast ultrasound. Core biopsy was performed under ultrasound guidance or clinically by a breast surgeon/ radiologist for BI-RADS category 3,4,5 lesions. STATISTICAL METHODS: Chi square test was done to show the strength of association of imaging findings and histopathology results of core biopsy. RESULTS: 437 patients were symptomatic and 30 patients had screen detected abnormalities. The positive predictive value for BI-RADS 5 lesions for malignancy is 93.25% and the negative predictive value of BI-RADS category 3 lesions for cancer is 98.4%. False negative diagnosis on core biopsy was 0.85%. We were able to defer surgery in 60% of the patients with a clear radiological and pathological benign diagnosis. CONCLUSION: The PPV and NPV for cancer is high with needle core biopsy in BI-RADS 3,4,5 lesions. Where there is no discordance between clinical, radiology and pathology findings, surgery can be avoided in benign lesions. While in resource poor countries FNAC continues to be a valuable method in the diagnosis of palpable and non palpable breast lesions, the practice of needle core biopsy provides the most accurate and optimal diagnostic information.

Expression of matrix metalloproteinases in human breast cancer tissues.

BACKGROUND: Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients. OBJECTIVE: The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with normal breast tissues. PATIENTS AND METHODS: We collected 39 breast cancer samples (24 grade II and 15 grade III) along with 16 normal breast tissues from outside the tumor margin during cancer removal surgery. The samples were analysed for the expression of all known MMPs using real-time quantitative PCR. RESULTS: The results indicate that mRNA expressions of MMP-1, -9,-11,-15,-24 and -25 were upregulated in breast cancer tissues when compared to normal breast tissues. But, the mRNA expressions of MMP-10 and MMP-19 were downregulated in cancer tissue. In membrane associated MMPs like MMP-15 and MMP-24 we found a grade dependent increase of their mRNA expression. CONCLUSION: Our studies demonstrate that MMPs are differentially regulated in breast cancer tissues and they might play various roles in tumor invasion, metastasis and angiogenesis. Thus, MMPs are of immense value to be studied as diagnostic markers and drug target.

Images: granular cell tumour of the breast mimics a malignancy.

Five percent of granular cell tumour occurs in the breast. They are benign in nature but mimick a carcinoma on imaging (mammography and breast ultrasound). We present radilogical and histopathological images of granular cell tumour in the breast.