Tata Memorial Centre Evidence Based Management of Breast cancer.

ABSTRACT: The incidence of breast cancer is increasing rapidly in urban India due to the changing lifestyle and exposure to risk factors. Diagnosis at an advanced stage and in younger women are the most concerning issues of breast cancer in India. Lack of awareness and social taboos related to cancer diagnosis make women feel hesitant to seek timely medical advice. As almost half of women develop breast cancer at an age younger than 50 years, breast cancer diagnosis poses a huge financial burden on the household and impacts the entire family. Moreover, inaccessibility, unaffordability, and high out-of-pocket expenditure make this situation grimmer. Women find it difficult to get quality cancer care closer to their homes and end up traveling long distances for seeking treatment. Significant differences in the cancer epidemiology compared to the west make the adoption of western breast cancer management guidelines challenging for Indian women. In this article, we intend to provide a comprehensive review of the management of breast cancer from diagnosis to treatment for both early and advanced stages from the perspective of low-middle-income countries. Starting with a brief introduction to epidemiology and guidelines for diagnostic modalities (imaging and pathology), treatment has been discussed for early breast cancer (EBC), locally advanced, and MBC. In-depth information on loco-regional and systemic therapy has been provided focusing on standard treatment protocols as well as scenarios where treatment can be de-escalated or escalated.

Prospective Study of Incidence and Impact of Comorbidities on Breast Cancer Survival from India.

PURPOSE: To report comorbidity burden in newly-diagnosed treatment-naïve breast cancer patients and its effect on survival. METHODS: Prospective observational study in which demographic, comorbidity and outcome data from a consecutive cohort of patients diagnosed and treated between September 2019 to September 2021 were collected. Charlson Comorbidity Index (CCI) score was calculated for all and proportion of each comorbidity was determined at diagnosis (baseline), at conclusion and six-months post-treatment. Univariate and multivariate analysis was done for impact of various demographic and disease-related factors on the incidence of comorbidities as well as on progression free survival (PFS) and overall survival (OS). RESULTS: Out of five hundred patients who consented for the study, 416 patients completed planned treatment and only 206 patients had physical follow-up due to COVID-19 pandemic. Incidence of comorbidity at the three time-points was 24%, 32% and 26% respectively. The difference was significant compared to baseline at both the time-points (p<0.05). Hypertension and diabetes were the most common types (incidence 15%-21% and 12-18% respectively) of comorbidities. Advancing age, post-menopauusal status and not being married were significant factors for presence of comorbidities. Median follow-up was 27 months (95% CI 26.25-28.55 months). Presence of multiple comorbidities was a poor prognostic factor for both PFS (2-yr PFS 85% vs 77%) and OS (2-yr OS 89% vs 79%) (both p=0.04) but no such correlation for CCI score. CONCLUSION: Breast cancer treatment impacted incidence of comorbidities. Presence of multiple comorbidities had an adverse impact on survival. Hence, further research on treatment optimization is required in patients with substantial comorbidities.

Long-term outcomes and prognostic factors in elderly patients with breast cancer: single-institutional experience.

Introduction: Despite advances in treatment, there is rising mortality in elderly patients with breast cancer. We aimed to conduct an audit of non-metastatic elderly breast cancer patients to understand the predictors of outcome. Methods: Data collection was done from electronic medical records. All time-to-event outcomes were analysed using Kaplan-Meier method and compared using log-rank test. Univariate and multi-variate analysis of known prognostic factors was also done. Any p-value ≤0.05 was considered statistically significant. Results: A total of 385 elderly (>70 years) breast cancer patients (range 70-95 years) were treated at our hospital from January 2013 to December 2016. The hormone receptor was positive in 284 (73.8%) patients; 69 (17.9%) patients had over-expression of HER2-neu, while 70 (18.2%) patients had triple-negative breast cancer. A large majority of women (N = 328, 85.9%) underwent mastectomy while only 54 (14.1%) had breast conservation surgery. Out of 134 patients who received chemotherapy, 111 patients received adjuvant, while the remaining 23 patients received neoadjuvant chemotherapy. Only 15 (21.7%) patients of the 69 HER2-neu receptor-positive patients received adjuvant trastuzumab. Adjuvant radiation was given to 194 (50.3%) women based on the type of surgery and disease stage. Adjuvant hormone therapy was planned using letrozole in 158 (55.6%) patients, while tamoxifen was prescribed in 126 (44.4%). At the median follow up of 71.7 months, the 5-year overall survival, relapse-free survival, locoregional relapse-free survival, distant disease-free survival, breast cancer-specific survival were 75.3%, 74.2%, 84.8%, 76.1% and 84.5%. Age, tumour size, presence of lymphovascular invasion (LVSI) and molecular subtype emerged as independent predictors of survival on multi-variate analysis. Conclusion: The audit highlights the underutilisation of breast-conserving therapy and systemic therapy in the elderly. Increasing age and tumour size, presence of LVSI and molecular subtype were found to be strong predictors of outcome. The findings from this study will help to improve the current gaps in the management of breast cancer among the elderly.

CONcurrent ChEmotherapy and RadioTherapy in adjuvant treatment of breast cancer (CONCERT): a phase 2 study.

Purpose: This phase 2 study evaluated the safety of adjuvant chemoradiation (CTRT) for breast cancer. Methods: From April 2019 to 2020, 60 patients with stage II-III invasive breast cancer planned for adjuvant taxane-based chemotherapy and radiotherapy (RT) were accrued. Local ± regional (excluding the internal mammary nodal region) RT (40 Gy in 15 fractions ± boost) was started with the third cycle of an adjuvant taxane in a 3-weekly schedule or with the eighth cycle in a weekly schedule. Results: Thirty-six patients received 3-weekly paclitaxel regimen and 24 received weekly paclitaxel regimen. The commonly used technique was three-dimensional conformal RT which was employed in 58% of patients. Regional RT, including the medial supraclavicular region, was done in 42 patients (70%). No dose-limiting (grade 3 or 4) toxicity was documented and all patients completed CTRT without any treatment interruption. The median ejection fraction pre and post CTRT 6 months was 60% (p = 0.177). The median value of cardiac enzyme (Troponin T ng/L) decreased from 37 to 20 (p = 0.009) post CTRT 6 months. Of the 54 patients who underwent the pulmonary function tests, there was no significant difference in various parameters like functional vital capacity (FVC) (2.29 versus 2.2 L, p = 0.375), forced expiratory volume at 1 second (FEV1) (1.86; 1.82; p = 0.365), FEV1/FVC (81.5; 81.43; p = 0.9) and diffusion lung capacity for carbon monoxide (88.3; 87.6; p = 0.62). At a median follow-up of 34 months, the 3-year actuarial rate of disease-free survival and overall survival was 75% and 98.3%, respectively. Quality of life scores (QOL) improved after treatment for most of the domains comparable to the pre-RT scores. Conclusion: Taxane-based adjuvant CTRT is a safe option and results in minimal toxicity and excellent compliance. It has favourable impact on cardio-pulmonary profile and QOL scores.

Can knowledge based treatment planning of VMAT for post-mastectomy locoregional radiotherapy involving internal mammary chain and supraclavicular fossa improve performance efficiency?

Introduction: To validate and evaluate the performance of knowledge-based treatment planning for Volumetric Modulated Arc Radiotherapy for post-mastectomy loco-regional radiotherapy. Material and methods: Two knowledge-based planning (KBP) models for different dose prescriptions were built using the Eclipse RapidPlanTM v 16.1 (Varian Medical Systems, Palo Alto, USA) utilising the plans of previously treated patients with left-sided breast cancer who had undergone irradiation of the left chest wall, internal mammary nodal (IMN) region and supra-clavicular fossa (SCF). Plans of 60 and 73 patients were used to generate the KBP models for the prescriptions of 40 Gy in 15 fractions and 26 Gy in 5 fractions, respectively. A blinded review of all the clinical plans (CLI) and KBPs was done by two experienced radiation oncology consultants. Statistical analysis of the two groups was also done using the standard two-tailed paired t-test or Wilcoxon signed rank test, and p<0.05 was considered significant. Results: A total of 20 metrics were compared. The KBPs were found to be either better (6/20) or comparable (10/20) to the CLIs for both the regimens. Dose to heart, contralateral breast,contralateral lung were either better or comparable in the KBP plans except of ipsilateral lung. Mean dose (Gy) for the ipsilateral lung are significantly (p˂0.001) higher in KBP though the values were acceptable clinically. Plans were of similar quality as per the result of the blinded review which was conducted by slice-by-slice evaluation of dose distribution for target coverage, overdose volume and dose to the OARs. However, it was also observed that treatment times in terms of monitoring units (MUs) and complexity indices are more in CLIs as compared with KBPs (p<0.001). Discussion: KBP models for left-sided post-mastectomy loco-regional radiotherapy were developed and validated for clinical use. These models improved the efficiency of treatment delivery as well as work flow for VMAT planning involving both moderately hypo fractionated and ultra-hypo fractionated radiotherapy regimens.

Health-Related Quality of Life (HRQoL) Using EQ-5D-5L: Value Set Derived for Indian Breast Cancer Cohort.

OBJECTIVE: The purpose of this study was to report quality of life of newly diagnosed breast cancer patients from India in a large cohort using the EQ-5D-5L instrument. METHODS: The study used longitudinal data of 500 breast cancer and 200 non-cancer subjects registered at our centre, during June 2019 and March 2022. The EQ-5D-5L and EQ-VAS instruments were used to measure and compare utility scores among cancer and non-cancer subjects. Descriptive statistics were analyzed and Tobit regression model were used to confirm the predictors of the utility score. RESULTS: The cancer subjects had a mean EQ-ED-5L utility score of 0.8703 (SD=0.121), 0.8745 (SD=0.094) and 0.8902 (SD=0.107) at the time of baseline, completion and follow up surveys respectively.  EQ-5D-5L values had significantly worsened after diagnosis of cancer as compared to the non-cancer cohort (0.87 vs. 0.93, p value 0.000). EQ-5D-5L utility scores as per stage for the cancer cohort were 0.88, 0.86 and 0.83 respectively for stage I-II, III and IV. Similarly, the EQ-VAS scores for stage I-II, III and IV were 74.9, 72.6 and 73.2 respectively. Multivariate analysis confirmed strong association of age, religion and income with the utility-values. CONCLUSION: This is the first longitudinal study reporting the utility scores derived from a large cohort of breast cancer patients demonstrating lower utility scores compared to non-cancer cohort. The utility scores also improve post treatment completion for cancer patients and decrease with higher stage at diagnosis. This information will be useful for future health economic research in India pertaining to breast cancer.

Socio-economic variations of breast cancer treatment and discontinuation: a study from a public tertiary cancer hospital in Mumbai, India.

BACKGROUND: The study examined the socio-economic variation of breast cancer treatment and treatment discontinuation due to deaths and financial crisis. METHODS: We used primary data of 500 patients with breast cancer sought treatment at India's one of the largest cancer hospital in Mumbai, between June 2019 and March 2022. This study is registered on the Clinical Trial Registry of India (CTRI/2019/07/020142). Kaplan-Meier method and Cox-hazard regression model were used to calculate the probability of treatment discontinuation. RESULTS: Of the 500 patients, three-fifths were under 50 years, with the median age being 46 years. More than half of the patients were from outside of the state and had travelled an average distance of 1,044 kms to get treatment. The majority of the patients were poor with an average household income of INR15,551. A total of 71 (14%) patients out of 500 had discontinued their treatment. About 5.2% of the patients died and 4.8% of them discontinued treatment due to financial crisis. Over one-fourth of all deaths were reported among stage IV patients (25%). Patients who did not have any health insurance, never attended school, cancer stage IV had a higher percentage of treatment discontinuation due to financial crisis. Hazard of discontinuation was lower for patients with secondary (HR:0.48; 95% CI: 0.27-0.84) and higher secondary education (HR: 0.42; 95% CI: 0.19-0.92), patients from rural area (HR: 0.79; 95% CI: 0.42-1.50), treated under general or non-chargeable category (HR: 0.60; 95% CI:0.22-1.60) while it was higher for the stage IV patients (HR: 3.61; 95% CI: 1.58-8.29). CONCLUSION: Integrating breast cancer screening in maternal and child health programme can reduce delay in diagnosis and premature mortality. Provisioning of free treatment for poor patients may reduce discontinuation of treatment.

Cancer care continuum at a tertiary care centre in India during the Covid-19 pandemic and nationwide lockdown: Healthcare delivery through telemedicine.

Background The Covid-19 pandemic and subsequent lockdown in India caused disruptions in cancer treatment due to the restriction on movement of patients. We aimed to maintain continuity in cancer treatment during the lockdown through teleconsultations. We tried to reach out to our patients using telephonic consultations by establishing a Teleconsult Centre facility run by a team of doctors and patient navigators. Methods We telephonically contacted all patients who had outpatient appointments from 23 March to 30 April 2020 at our centre through the Teleconsult Centre to understand their current circumstances, feasibility of follow-up, local resources and offered best possible alternatives to continue cancer treatment, if required. Results Of the 2686 patients scheduled for follow-up during this period, we could contact 1783 patients in 9 working days. Through teleconsultations, we could defer follow-ups of 1034 patients (57.99%, 95% confidence interval [CI] 55.6%-60.3%), thus reducing the need for patients to travel to the hospital. Change in systemic therapy was made in 75 patients (4.2%, 95% CI 3.3%-5.2%) as per the requirements and available resources. Symptoms suggestive of disease progression were picked up in 12 patients (0.67%, 95% CI 0.35%-1.17%), who were advised to meet local physicians. Conclusion Our study suggests that the majority of patients on follow-up can be managed with teleconsultation in times of crisis. Teleconsultation has the potential of being one of the standard methods of patient follow-up even during periods of normalcy.

Socio-economic and regional variation in breast and cervical cancer screening among Indian women of reproductive age: a study from National Family Health Survey, 2019-21.

BACKGROUND: In India, breast and cervical cancers account for two-fifths of all cancers and are predominantly prevalent among women in the reproductive age group. The Government of India recommended screening of breast and cervical cancer among women aged 30 years and over. This study examines the socio-economic and regional variations of breast and cervical screening among Indian women in the reproductive age. METHODS: A full sample of 707,119 women aged 15-49 and a sub-sample of 357,353 women aged 30-49 from National Family Health Survey-5 (2019-21) were used in the analysis. Self-reported ever screening for breast and cervical cancer for women aged 15-49 and women aged 30-49 were outcome variables. A set of socio-economic and risk factors associated with breast and cervical cancer screening were used as the predictors. Logistic regression was used to understand the significant correlates of cancer screening and, concentration index and concentration curve were used to assess the socio-economic inequality in breast and cervical cancer screening. RESULTS: The proportion of breast and cervical cancer screening among women aged 30-49 were 877 and 1965 per 100,000 women respectively. Cancer screening was lower among women who were poor, young, had lower educational attainment and resided in rural areas. The concentration index was 0.2 for ever screening of breast cancer and 0.15 for cervical cancer among women aged 30-49 years. The concertation curve for screening of both breast and cervical cancers was pro-rich. Women with higher educational attainment [OR:1.46, 95% CI: 1.31-1.62], aged 40-49 years [OR:1.35; 95% CI: 1.28-1.43], resided in the western [OR:1.62; 95% CI:1.4-1.87] or southern [OR:6.66; 95% CI:5.93-7.49] region had significantly higher odds of up taking either of the screening. The pattern of breast and cervical cancer screening among women aged 15-49 was similar to that of women 30-49. CONCLUSION: The overall proportion of cancer screening among women in 30-49 age group is low in India. Early screening and treatment can reduce the burden of these cancers. Creating awareness and providing knowledge on cancer could be a key strategy for reducing the burden of breast and cervical cancers among women in the reproductive age in India.

Clinical Profile and Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer With Brain Metastases: Real-World Experience.

PURPOSE: There are sparse data in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases from real-world settings, especially where access to newer targeted therapies is limited. METHODS: This was a single institution, retrospective cohort study of patients with HER2-positive breast cancer diagnosed between January 2013 and December 2017 to have brain metastases and treated with any HER2-targeted therapy. The main objectives were to estimate progression-free survival (PFS) and overall survival (OS) from the time of brain metastases. RESULTS: A total of 102 patients with a median age of 52 (interquartile range, 45-57) years were included, of whom 63 (61.8%) had received one line and 14 (13.7%) had received two lines of HER2-targeted therapies before brain metastasis, 98 (96.1%) were symptomatic at presentation, 22 (25.3%) had solitary brain lesion, 22 (25.3%) had 2-5 lesions, and 43 (49.4%) had ≥ 5 lesions. Local treatment included surgical resection in nine (8.9%) and radiotherapy in all (100%) patients. The first HER2-targeted therapy after brain metastasis was lapatinib in 71 (68.6%), trastuzumab in 19 (18.6%), lapatinib and trastuzumab in three (2.9%), trastuzumab emtansine in four (3.9%), and intrathecal trastuzumab in five (4.9%) patients. At a median follow-up of 13.9 months, the median PFS and OS were 8 (95% CI, 6.2 to 9.8) months and 14 (95% CI, 10.8 to 17.2) months, respectively, with a 2-year OS of 25% (95% CI, 16.7 to 34.4). The median PFS in patients who received lapatinib-capecitabine regimen (n = 62) was 9.0 (95% CI, 7.3 to 10.7) months. CONCLUSION: There was a substantial clinical benefit of local and systemic therapy in patients with brain metastases and HER2-positive disease in a real-world setting with limited access to newer HER2-targeted drugs.

Adopting Health Economic Research in Radiation Oncology: A Perspective From Low- or Middle-Income Countries.

Establishing a new radiation therapy (RT) setup is resource-intensive as it involves substantial capital costs and the recruitment of a skilled workforce. It is essential to incorporate health economic analysis that estimates recurring and nonrecurring expenses on the basis of the national and local needs, infrastructure, and future projections. RT costing exercises can be especially relevant for low- or middle-income countries (LMICs) with more than 70% of the global cancer burden, with access to < 20% of the available resources. This review article summarizes the scope of RT costing exercises in LMICs, the hurdles in conducting them, and possible ways to circumvent them. The purpose of performing costing studies in RT lies in their utility to improve the efficiency of the investment while at the same time helping to address the issues of uniformity and equitable distribution of resources. This will help assess the net benefit from RT in terms of utility and outcome-linked parameters like Quality-Adjusted Life Years. There are numerous barriers to conducting economic evaluations in LMICs, including the lack of national costing values for equipment, data on manpower salary, cost for public and private setups, and indirect costs. The situation is further complicated because of the nonuniform pay structure, lack of an organizational framework, robust real-world data on outcomes, and nonavailability of country-specific reference utility values. Collaborative national efforts are required to collect all elements required to perform health technology assessments. Information from the national and hospital databases can be made available in the public domain to ease access and broader adoption of health economic end points in routine care. Although resource-intensive at the onset, costing studies and health economic assessments are essential for improving the coverage and quality of RT in LMICs.

Outcomes of non-metastatic triple negative breast cancers: Real-world data from a large Indian cohort.

BACKGROUND: Triple negative Breast tumor (TNBC) is an aggressive tumor with sparse data worldwide. METHODS: We analyzed non-metastatic TNBC from 2013 to 2019 for demographics, practice patterns, and survival by the Kaplan Meir method. Prognostic factors for OS and DFS were evaluated using Cox Proportional Hazard model estimator for univariate and multivariable analysis after checking for collinearity among the variables. RESULTS: There were 1297 patients with median age of 38 years; 41 (33.3%) among 123 tested were BRCA-positives. Among these 593 (45.7%) had stage III disease, 1279 (98.6%) were grade III, 165 (13.0%) had peri-nodal extension (PNE), 212 (16.0%) lympho-vascular invasion (LVI), and 21 (1.6%) were metaplastic; 1256 (96.8%) received chemotherapy including 820 (63.2%) neoadjuvant with 306 (40.0%) pCR. Grade ≥3 toxicities occurred in 155 (12.4%) including two deaths and 3 s-primaries. 1234 (95.2%) underwent surgery [722 (55.7%) breast conservations] and 1034 (79.7%) received radiotherapy. At a median follow-up of 54 months, median disease-free (DFS) was 92.2 months and overall survival (OS) was not reached. 5-year estimated DFS and OS was 65.9% and 80.3%. There were 259 (20.0%) failures; predominantly distant (204, 15.7%) - lung (51%), liver (31.8%). In multivariate analysis presence of LVI (HR-2.00, p-0.003), PNE (HR-2.09 p-0.003), older age (HR-1.03, p-0.002) and stage III disease (HR-4.89, p-0.027), were associated with poor OS. CONCLUSION: Relatively large contemporary data of non-metastatic TNBC confirms aggressive biology and predominant advanced stage presentation which adversely affects outcomes. The data strongly indicate the unmet need for early detection to optimize care.

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.

Ultrasound augments on-demand breast tumor radiosensitization and apoptosis through a tri-responsive combinatorial delivery theranostic platform.

Advanced inoperable triple-negative breast cancer (TNBC) comprises aggressive tumors with a modest pathological response to neoadjuvant chemotherapy. The concomitant use of chemoradiotherapy improves the pathological response rates. However, the dose-dependent systemic toxicity of clinical radiosensitizers with poor circulation half-life and limited passive bioavailability limits their clinical utility. We address these challenges by rationally designing a stealth and tumor microenvironment responsive nano-conjugate platform for the ultrasound-mediated on-demand spatio-temporal delivery of plant flavonoid curcumin as a combinatorial regimen with clinically approved paclitaxel for the neoadjuvant chemoradiotherapy of locally advanced triple-negative breast cancer (TNBC). Interestingly, the focused application of ultrasound at the orthotopic TNBC xenograft of NOD-SCID mice facilitated the immediate infiltration of nano-conjugates at the tumor interstitium, and conferred in vivo safety over marketed paclitaxel formulation. In addition, curcumin significantly potentiated the in vivo chemoradiotherapeutic efficacy of paclitaxel upon loading into nano-conjugates. This gets further enhanced by the concurrent pulse of ultrasound, as confirmed by PET-CT imaging, along with a significant improvement in the mice survival. The quadrapeutic apoptotic effect by the combination of paclitaxel, curcumin, radiation, and ultrasound, along with a reduction in the tumor microvessel density and cell proliferation marker, confers the broad chemo-radiotherapeutic potential of this regimen for radio-responsive solid tumors, as well as metastatic niches.

Unique challenges and outcomes of young women with breast cancers from a tertiary care cancer centre in India.

BACKGROUND: Young (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying. METHODS: The YBC treated with a curative intent between 2015 and 2016 at our institute were analysed. RESULTS: There were 1228 patients with a median age of 36 (12-40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) -III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0-131) months, 5-year overall and disease-free survival was 79.6% (76.8-82.5) and 59.1% (55.8-62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8-90.6), 77.3% (73.4-81.2), 69.7% (52.5-86.9) and disease-free survival was 94% (85.9-100), 65.9% (60.3-71.5), 55% (50.5-59.5), and 29.6% (14-45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6-86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients. CONCLUSION: More than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus.

Patient-reported quality of life with interstitial partial breast brachytherapy and external beam whole breast radiotherapy: a comparison using propensity-score matching.

PURPOSE: The aim of this study was to compare patient-reported quality of life (QOL) scores after accelerated partial breast irradiation (APBI) using interstitial brachytherapy vs. external beam whole breast radiotherapy (WBRT) for breast cancer. MATERIAL AND METHODS: Women with breast cancer treated with WBRT or APBI after breast conservation surgery were enrolled in this prospective study. Single cross-sectional QOL assessment was performed using EORTC QLQ-C30 and BR-23 questionnaires. Patients treated with APBI were propensity-score matched to similar cohort of patients treated with WBRT. QOL scores were analyzed for the entire unmatched cohort and compared between the two matched cohorts using Student's two-tailed t-test. P-value of < 0.05 was considered statistically significant, and a 10-point difference between mean scores was considered clinically meaningful. RESULTS: A total of 64 APBI patients were matched with 99 WBRT patients out of the entire study cohort of 320 cases. QOL scores for functional scales of QLQ-C30 were similar between the two groups for both matched and unmatched cohorts, while symptom scores of QLQ-C30 did not show any clinically significant difference. Functional scales of BR-23 did not show any clinical or statistically significant difference. Among symptom scales of BR-23, scores were similar for APBI and WBRT groups except for a worse score of "upset by hair loss" sub-scale in the brachytherapy group of the matched cohort (51.9 vs. 22.7, p = 0.006). CONCLUSIONS: Patients undergoing APBI reported similar QOL compared to WBRT when matched for various factors.

Multinational Study to Assess Stress Levels Among the Health Care Workers of Radiation Oncology Community at the Outset of the COVID-19 Pandemic.

PURPOSE: To evaluate stress levels among the health care workers (HCWs) of the radiation oncology community in Asian countries. METHODS: HCWs of the radiation oncology departments from 29 tertiary cancer care centers of Bangladesh, India, Indonesia and Nepal were studied from May 2020 to July 2020. A total of 758 eligible HCWs were identified. The 7-Item Generalized Anxiety Disorder, 9-Item Patient Health Questionnaire, and 22-Item Impact of Events Scale-Revised were used for assessing anxiety, depression, and post-traumatic stress disorder. Univariate and multivariate analysis was done to identify the causative factors affecting mental health. RESULTS: A total of 758 participants from 794 HCWs were analyzed. The median age was 31 years (IQR, 27-28). The incidence of moderate to severe levels of anxiety, depression, and stress was 34.8%, 31.2%, and 18.2%, respectively. Severe personal concerns were noticed by 60.9% of the staff. On multivariate analysis, the presence of commonly reported symptoms of COVID-19 during the previous 2 weeks, contact history (harzard ratio [HR], 2.04; CI, 1.15 to 3.63), and compliance with precautionary measures (HR, 1.69; CI, 1.19 to 2.45) for COVID-19 significantly predicted for increasing anxiety (HR, 2.67; CI, 1.93 to 3.70), depression (HR, 3.38; CI 2.36 to 4.84), and stress (HR, 2.89; CI, 1.88 to 4.43) (P < .001). A significant regional variation was also noticed for anxiety, stress, and personal concerns. CONCLUSION: This survey conducted during the COVID-19 pandemic revealed that a significant proportion of HCWs in the radiation oncology community experiences moderate to severe levels of anxiety, depression, and stress. This trend is alarming and it is important to identify and intervene at the right time to improve the mental health of HCWs to avoid any long-term impacts.

Economic Distress of Breast Cancer Patients Seeking Treatment at a Tertiary Cancer Center in Mumbai during COVID-19 Pandemic: A Cohort Study.

BACKGROUND: Cancer treatment during nationwide lockdown due to the COVID-19 pandemic has posed several challenges in the delivery of cancer care and carries tremendous potential sequel of impoverishing the households. This study aims to examine the economic distress faced by breast cancer patients receiving treatment at Tata Memorial Center (TMC) Mumbai, India during the nationwide lockdown initiated in March 2020 following the outbreak of COVID-19. METHODS: A total of 138 non-metastatic breast cancer patients who were accrued in this study at TMC before imposing of lockdown, and their treatment was impacted because of the COVID-19 outbreak, were interviewed. Telephonic interviews were conducted using a structured schedule which contained information on household and demographic characteristics of the patients, knowledge about COVID-19, their daily expenditure for treatment, difficulties faced during lockdown and how they met expenditures. Descriptive statistics and logistic regression were used in the analyses. RESULTS: The average monthly expenditure of cancer patients had increased by 32% during the COVID-19 period while the mean monthly household income was reduced by a quarter. More than two-thirds of the patients had no income during the lockdown. More than half of the patients met their expenditure by borrowing money, 30% of the patients used their savings, 28% got charity and 25% used household income. About 81% of the patients had reported shortage of money, 32%  reported shortage of food and 28% reported shortage of medicine. The distress financing was significantly higher among patients receiving treatment in Mumbai compared to those receiving treatment at their native cities (67% vs. 46%), patients under 40 years of age, illiterate, currently married, Muslim and staying at a rented house. CONCLUSION: The incremental expenditure coupled with reduced or no income due to the closure of economic activities in the country imposed severe financial stress on breast cancer patients.

Pregnancy associated breast cancer (PABC): Report from a gestational cancer registry from a tertiary cancer care centre, India.

BACKGROUND: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration. METHODS: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC. RESULTS: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones. CONCLUSION: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.