Survival outcomes with 12 weeks of adjuvant or neoadjuvant trastuzumab in breast cancer.

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

Prognostic factors in node negative premenopausal women treated with breast conserving therapy without adjuvant systemic therapy.

PURPOSE: To study the prognostic factors in node negative premenopausal women treated with breast conserving therapy (BCT) without any adjuvant systemic therapy. METHODS: Of the 1022 women treated with BCT at Tata Memorial Hospital, there was a cohort of 175 women who were premenopausal, node negative and had not received any adjuvant systemic therapy. BCT consisted of wide excision, complete axillary clearance, whole breast radiotherapy (45 Gy in 25 fractions) with 6 MV photons plus tumour bed boost either with brachytherapy or electrons. RESULTS: The median age at presentation was 38 years (range 22-51 years) and the median pathological tumour size was 3 cm (1-5 cm). The 5-year actuarial local control rate was 89.5% and the overall survival (OS) was 88%. On univariate analysis, lymphovascular invasion (LVI) was the only prognostic factor affecting all failures and disease-free survival. The 5-year local control rate in absence of LVI was 93.5% in contrast to 76.5% (p=0.0098) when LVI was present. Similarly, the OS in absence of LVI was 91% in contrast to 74% in presence of LVI (p=0.02). On multivariate analysis, LVI was the independent prognostic factor affecting the disease-free survival (p=0.001; 95% CI: 1.46-4.96). CONCLUSION: LVI emerged as the most important prognostic factor for node negative premenopausal women not receiving adjuvant systemic therapy. There is a need to take into consideration the presence of LVI while deciding adjuvant systemic therapy in T1N0 patients.

Safety and feasibility of breast conserving therapy in Indian women: two decades of experience at Tata Memorial Hospital.

PURPOSE: The NIH consensus statement on the management of breast cancer has highlighted the paucity of outcome data in non-Caucasian women. Treatment outcome and factors determining it in a large cohort of ethnic Indian women treated with breast conserving therapy (BCT) at Tata Memorial Hospital are reported here. MATERIALS AND METHODS: During 1980-2000, 1,022 pathological Stage I/II breast cancer patients (median age 43 years) underwent BCT (wide excision, complete axillary clearance, whole breast radiotherapy with 6 MV photons plus tumor bed boost, +/-systemic therapy). Median pathological tumor size was 3 cm (1-5 cm). Axillary node metastases were found in 39% women. Of the 938 patients with IDC, 70% were Grade III and in patients where receptor status was known, 209/625 (33%) were ER positive and 245/591 (41%) were PR positive. RESULTS: The 5- and 10-year actuarial overall survival was 87% and 77% and disease-free survival was 76% and 68%, respectively. Actuarial 5-year local and locoregional control rates were 91% and 87%, respectively. Cosmesis was good or excellent in 78% women. Independent adverse prognostic factors for local recurrence were, age<40 years, axillary node metastasis, lymphovascular invasion (LVI), and adjuvant systemic therapy; for locoregional recurrence-inner quadrant tumor, axillary node metastasis, and LVI; for survival-LVI and axillary node metastasis. CONCLUSION: Compared to Caucasians, these Indian women undergoing BCT were younger, had larger, higher grade, and receptor negative tumors. Comparable local control and survival was obtained by using stringent quality assurance in the diagnostic and therapeutic protocol. BCT, a resource intense treatment is safe for selected and motivated patients undergoing treatment at centers with adequate facilities and expertise even in countries with limited resources.

Profile of prognostic factors in 1022 Indian women with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. METHODS AND MATERIALS: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). RESULTS: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women. The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age < or =40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). CONCLUSION: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment.

Dosimetric study of optimal beam number and arrangement for treatment of nasopharyngeal carcinoma with intensity-modulated radiation therapy.

The purpose of this dosimetric study was to evaluate the effect of beam number and arrangement on the dose distribution with intensity-modulated radiation therapy in patients with nasopharyngeal cancer. Computed tomography data sets of seven patients who were treated for nasopharyngeal carcinoma at the Peter MacCallum Cancer Centre were used for the present dosimetric study. The dose planned was 70 Gy in 7 weeks for the gross nasopharyngeal and nodal disease and the biological equivalents of 60 Gy in 6 weeks for the high-risk and 50 Gy in 5 weeks for the low-risk nodal disease. A plan using seven fields was compared to that using nine fields in all patients. Plans were assessed on the dose to the planning target volume (PTV) and the degree of parotid sparing achieved by evaluating both dose-volume histograms (DVH) and axial slices. Seven fields (three anterior and four posterior) provide good PTV coverage and satisfactory parotid sparing in patients with localized nasopharyngeal lesions. Nine fields appear to be better for tumours with significant posterolateral parapharyngeal extension. Parotid sparing is consistently better with nine fields. Both DVH and axial slices need to be evaluated before accepting any plan.