A Questionnaire Survey of Current Practice in the Management of Internal Mammary Lymph Nodes in Breast Cancer.

Nita S. NairBackground Radiotherapy (RT) is an important modality in the management of breast cancers (BC). Large randomized trials have suggested that prophylactic regional nodal irradiation inclusive of internal mammary lymph nodes (IMLN) reduces BC-related mortality. However, the adoption of IMLN-RT has been variable due to relative benefits and toxicity concerns. Methods A survey was emailed to radiation oncologists (ROs) across the country wherein they were asked about their practice regarding IMLN-RT in BC. Results We received 128 responses, which included radiation oncologists across both private institutions (PIs) and government institutions (GIs). Fifty-six (43.8%) routinely offer prophylactic(p) IMLN-RT and an additional 15 (11.71%) suggested they would have offered it in the absence of logistic constraints. Almost all, 121 (94.5%) radiate the IMLN in case of radiologically positive lymph nodes (LNs). Fifty-six ROs (43.8%) offered prophylactic IMLN-RT in node-negative disease. Among those who did not offer IMLN-RT, most (84.72%) felt the clinical evidence was equivocal. Of the 56 who offered pIMLN-RT, 34/56 (60.71%) offered to locally advanced tumors, 20/56 (35.71%) offered to all inner and central tumors (ICQT), 29/56 (51.78%) to > 4 axillary LN-positive and 9/56 (16.07%) to any axillary LN-positive. The majority, i.e., 36/56 (64.28%) radiated upper three intercostal spaces, 9 (16.07%) radiated upper five intercostal spaces, and 6 (10.9%) decided based on tumor location, while 5 (9%) irradiated one space below the involved space. Overall, simulation-based planning was undertaken in 99% of PIs as opposed to 89% of GIs ( p = 0.03). The majority of ROs, i.e., 92 (72.4%) preferred IMRT to IMLN-RT. In addition, the surgical approach to IMLN was practiced by surgeons at 18 (14%) centers, of which 13 (72.22%) operated the IMLN when radiologically evident. The IMLN dissection was preferentially performed for second and third intercostal spaces as suggested in 10 (55.55%) responses, while 8 (44.44%) performed thoracoscopic dissection of the IMLN chain. The distribution of prophylactic, definitive IMLN-RT, and IMLN dissection did not differ significantly between GI and PI ( p = NS). Conclusion pIMLN-RT is still not the standard protocol in most centers citing equivocal evidence in the literature. Logistics, though different in GIs and PIs, did not impact the decision of pIMLN-RT. Further efforts would be required to standardize practice in IMLN across India.

Towards equitable AI in oncology.

Artificial intelligence (AI) stands at the threshold of revolutionizing clinical oncology, with considerable potential to improve early cancer detection and risk assessment, and to enable more accurate personalized treatment recommendations. However, a notable imbalance exists in the distribution of the benefits of AI, which disproportionately favour those living in specific geographical locations and in specific populations. In this Perspective, we discuss the need to foster the development of equitable AI tools that are both accurate in and accessible to a diverse range of patient populations, including those in low-income to middle-income countries. We also discuss some of the challenges and potential solutions in attaining equitable AI, including addressing the historically limited representation of diverse populations in existing clinical datasets and the use of inadequate clinical validation methods. Additionally, we focus on extant sources of inequity including the type of model approach (such as deep learning, and feature engineering-based methods), the implications of dataset curation strategies, the need for rigorous validation across a variety of populations and settings, and the risk of introducing contextual bias that comes with developing tools predominantly in high-income countries.

Out-of-pocket payment and financial risk protection for breast cancer treatment: a prospective study from India.

Background: Available data on cost of cancer treatment, out-of-pocket payment and reimbursement are limited in India. We estimated the treatment costs, out-of-pocket payment, and reimbursement in a cohort of breast cancer patients who sought treatment at a publicly funded tertiary cancer care hospital in India. Methods: A prospective longitudinal study was conducted from June 2019 to March 2022 at Tata Memorial Centre (TMC), Mumbai. Data on expenditure during each visit of treatment was collected by a team of trained medical social workers. The primary outcome variables were total cost (TC) of treatment, out-of-pocket payment (OOP), and reimbursement. TC included cost incurred by breast cancer patients during treatment at TMC. OOP was defined as the total cost incurred at TMC less of reimbursement. Reimbursement was any form of financial assistance (cashless or repayment), including social health insurance, private health insurance, employee health schemes, and assistance from charitable trusts, received by the patients for breast cancer treatment. Findings: Of the 500 patients included in the study, 45 discontinued treatment (due to financial or other reasons) and 26 died during treatment. The mean TC of breast cancer treatment was ₹258,095/US$3531 (95% CI: 238,225, 277,934). Direct medical cost (MC) accounted for 56.3% of the TC. Systemic therapy costs (₹50,869/US$696) were higher than radiotherapy (₹33,483/US$458) and surgery costs (₹25,075/US$343). About 74.4% patients availed some form of financial assistance at TMC; 8% patients received full reimbursement. The mean OOP for breast cancer treatment was ₹186,461/US$2551 (95% CI: 167,666, 205,257), accounting for 72.2% of the TC. Social health insurance (SHI) had a reasonable coverage (33.1%), followed by charitable trusts (29.6%), employee health insurance (5.1%), private health insurance (4.4%) and 25.6% had no reimbursement. But SHI covered only 40.1% of the TC of treatment compared to private health insurance that covered as much as 57.1% of it. Both TC and OOP were higher for patients who were younger, belonged to rural areas, had a comorbidity, were diagnosed at an advanced stage, and were from outside Maharashtra. Interpretation: In India, the cost and OOP for breast cancer treatment are high and reimbursement for the treatment flows from multiple sources. Though many of the patients receive some form of reimbursement, it is insufficient to prevent high OOP. Hence both wider insurance coverage as well as higher cap of the insurance packages in the health insurance schemes is suggested. Allowing for the automatic inclusion of cancer treatment in SHI can mitigate the financial burden of cancer patients in India. Funding: This work was funded by an extramural grant from the Women's Cancer Initiative and the Nag Foundation and an intramural grant from the International Institute of Population Sciences, Mumbai.

Surgical Tumor Resection Deregulates Hallmarks of Cancer in Resected Tissue and the Surrounding Microenvironment.

Surgery exposes tumor tissue to severe hypoxia and mechanical stress leading to rapid gene expression changes in the tumor and its microenvironment, which remain poorly characterized. We biopsied tumor and adjacent normal tissues from patients with breast (n = 81) and head/neck squamous cancers (HNSC; n = 10) at the beginning (A), during (B), and end of surgery (C). Tumor/normal RNA from 46/81 patients with breast cancer was subjected to mRNA-Seq using Illumina short-read technology, and from nine patients with HNSC to whole-transcriptome microarray with Illumina BeadArray. Pathways and genes involved in 7 of 10 known cancer hallmarks, namely, tumor-promoting inflammation (TNF-A, NFK-B, IL18 pathways), activation of invasion and migration (various extracellular matrix-related pathways, cell migration), sustained proliferative signaling (K-Ras Signaling), evasion of growth suppressors (P53 signaling, regulation of cell death), deregulating cellular energetics (response to lipid, secreted factors, and adipogenesis), inducing angiogenesis (hypoxia signaling, myogenesis), and avoiding immune destruction (CTLA4 and PDL1) were significantly deregulated during surgical resection (time points A vs. B vs. C). These findings were validated using NanoString assays in independent pre/intra/post-operative breast cancer samples from 48 patients. In a comparison of gene expression data from biopsy (analogous to time point A) with surgical resection samples (analogous to time point C) from The Cancer Genome Atlas study, the top deregulated genes were the same as identified in our analysis, in five of the seven studied cancer types. This study suggests that surgical extirpation deregulates the hallmarks of cancer in primary tumors and adjacent normal tissue across different cancers. IMPLICATIONS: Surgery deregulates hallmarks of cancer in human tissue.

Validation of PREDICT Version 2.2 in a Retrospective Cohort of Indian Women With Operable Breast Cancer.

PURPOSE: Online prediction models that use known prognostic factors in breast cancer (BC) are routinely used to assist in decisions for adjuvant therapy. PREDICT Version 2.2 (P2.2) is one such online tool, which uses tumor size, lymph node involvement, grade, age, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, and Ki67. We performed an external validation in a retrospective cohort of patients treated at a tertiary center in India. METHODS: Women with operable BC between 2008 and 2016 with nonmetastatic, T1-T2 invasive, and HER2 receptor-negative BC and with available 5-year overall survival (OS) data were selected. Median predicted 5-year OS rates were used to calculate predicted events for the whole cohort and subgroups. The chi-square test was used to evaluate the goodness of fit of the tool. RESULTS: Of 11,760 cases registered between 2008 and 2016, 2,783 (23.66%) eligible patients with a median age of 50 (26-70) years and a median pT size of 2.5 (0.1-5) cm, 2,037 (73.19%) with grade 3 tumors, 1,172 (42.11%) with node-positive disease, 817 (29.35%) with triple-negative breast cancer, and 1,966 (70.64%) with HR-positive BC were included in the analysis. The observed 5-year OS and predicted 5-year OS in the whole cohort were 94.8% and 90.00%, respectively, with an absolute difference of 4.8% (95% CI, 3.417 to 6.198, P < .001). The observed 5-year OS and predicted 5-year OS were also different in various subgroups. CONCLUSION: PREDICT version 2.2 overestimated the number of deaths, with lower predicted 5-year OS compared with the observed value, in this retrospective Indian cohort. The reasons for this discrepancy could be differing biologic characteristics and possible selection bias in our cohort. We recommend a prospective validation of PREDICT in Indian patients and advocate caution in its use until such validation is achieved.

Retrospective audit of the yield of internal mammary lymph node dissection and literature review in the management of breast cancer.

BACKGROUND: Treatment of lymph node basins is prognostic and therapeutic for axillary lymph nodes (ALN) as well as internal mammary lymph nodes (IMLNs) in breast cancer. IMLNs can be the first echelon node for the inner/central quadrants of the breast. We evaluated the yield of IMLN dissection (IMLND) mainly in patients with inner and central tumors. METHODS: IMLND was performed in 199 patients between 2000 and 2018, 127 of whom had tumors in the inner/ central quadrants. Clinico-pathological data were retrieved from Electronic Medical Records (EMR). RESULTS: The median age was 50 (range: 24-81). Primary surgery was performed in 82 (41.2%), while 117 (58.8%) were operated post-chemotherapy. Overall, 124/199 (62.3%) had nodes identified in the specimen, more often in primary (61/82, 74.4%) than post-chemotherapy settings (63/117, 53.8%) (P = 0.003). A median of 1 (average: 1.24, range: 0-7) lymph nodes was dissected, and 1 (average: 1.5, range: 1-4) was involved. IMLN was positive in 46/199 (23.1%) patients, not significantly different in primary (21/82, 25.6%) versus post-chemotherapy (25/117, 21.4%) settings (P = 0.545). IMLN was involved in 44.8% of patients with ≥4 involved ALN and 8.2% with uninvolved ALN (P < 0.001). In the absence of ALN involvement and <2cm pT size, 9% of patients had positive IMLN in inner/central quadrant tumors. In univariate analysis, ALN positivity (P < 0.001), pT size (P = 0.023), and grade (P = 0.041) in primary and ALN involvement (P = 0.011) in post-chemotherapy patients were associated with IMLN involvement. On logistic regression, tumor size (OR: 13.914, P = 0.017) and ALN involvement (OR: 11.400, P = 0.005) in primary surgery and ALN involvement (OR: 7.294, P = 0.003) in post-chemotherapy patients correlated with IMLN involvement. CONCLUSIONS: In inner/central quadrant tumors, IMLN is more likely involved with high ALN burden and tumor size >2 cm, whereas those with ≤2cm inner/central quadrant tumors and negative ALN have <10% probability of IMLN involvement.

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.

Effectiveness of a Decision Aid Plus Standard Care in Surgical Management Among Patients With Early Breast Cancer: A Randomized Clinical Trial.

Importance: Patients with early breast cancer must choose between undergoing breast conservation surgery or mastectomy. This decision is often difficult as there are trade-offs between breast conservation and adverse effects, and women with higher decisional conflict have a harder time choosing the therapy that suits their preferences. Objective: To study the impact of a decision aid with a patient preference assessment tool for surgical decision-making on patients' decisional conflict scale (DCS) score. Design, Setting, and Participants: This 3-group randomized clinical trial was conducted between June 2017 and December 2019 at a single high-volume tertiary care cancer center in Mumbai, India. A research questionnaire comprising 16 questions answered on a Likert scale (from 1, strongly agree, to 5, strongly disagree) was used to measure DCS scores and other secondary psychological variables, with higher scores indicating more decisional conflict. The Navya Patient Preference Tool (Navya-PPT) was developed as a survey-based presentation of evidence in an adaptive, conjoint analysis-based module for and trade-offs between cosmesis, adverse effects of radiotherapy, and cost of mandatory radiation following breast-conserving surgery. Adult patients with histologically proven early breast cancer (cT1-2, N0-1) who were eligible for breast-conserving surgery as per clinicoradiological assessment were included. Those who were pregnant or unable to read the research questionnaire or who had bilateral breast cancer were excluded. Data were analyzed from January to June 2020. Interventions: Patients were randomized 1:1:1 to study groups: standard care including clinical explanation about surgery (control), standard care plus the Navya-PPT provided to the patient alone (solo group), and standard care plus the Navya-PPT provided to the patient and a caregiver (joint group). Main Outcomes and Measures: The primary end point of the study was DCS score. The study was 80% powered with 2-sided α = .01 to detect an effect size of 0.25 measured by Cohen d, F test analysis of variance, and fixed effects. Results: A total of 245 female patients (median [range] age, 48 [23-76] years) were randomized (82 to control, 83 to the solo group, and 80 to the joint group). The median (range) pathological tumor size was 2.5 (0-6) cm. A total of 153 participants (62.4%) had pN0 disease, 185 (75.5%) were hormone receptor positive, 197 (80.4%) were human epidermal growth factor receptor 2 negative, 144 (58.6%) were of middle or lower socioeconomic status, and 114 (46.5%) had an education level lower than a college degree. DCS score was significantly reduced in the solo group compared with control (1.34 vs 1.66, respectively; Cohen d, 0.50; SD, 0.31; P < .001) and the joint group compared with control (1.31 vs 1.66, respectively; Cohen d, 0.54; SD, 0.31; P < .001). Conclusions and Relevance: The results of this study demonstrated lower decisional conflict as measured by DCS score following use of the online, self-administered Navya-PPT among patients with early breast cancer choosing between breast-conserving surgery vs mastectomy. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/11/010480.

Accuracy of Intraoperative Frozen Section Analysis of Lymph Nodes in Women Undergoing Axillary Sampling for Treatment of Breast Cancer: Single Institution Audit.

BACKGROUND: Axillary lymph node (LN) positivity is an important prognostic factor in breast cancer. Almost 30% clinically node negative (cN0) early breast cancers have positive nodes on pathology, wherein an axillary dissection is done as a second stage surgery. Intra operative frozen section (FS) potentially avoids redo surgery. MATERIALS AND METHODS: We performed a retrospective audit for the false negative rate of intraoperative FS, from 2014 to 2018. All cN0 women undergoing upfront surgery, who underwent low axillary sampling (LAS) with FS were included. RESULTS: Of 22,854 breast cancer cases, 2230 underwent LAS, of which 877 were node positive. Intraoperative FS was negative in 1423/2230 (63.81%) cases, of which 71/1423 (4.98%) were false negative, and came positive on final histopathology report (HPR). These 71 women had a median of 5 nodes (mean 4.85) dissected on FS (range 1-12) with a median 1 (mean 1.3) node positive (range 1-6) on HPR. The sensitivity of FS was 91.89% (95% CI, 89.89-93.62), with a negative predictive value of 95.01% (95% CI, 93.84-95.97), accuracy of 96.73% (95% CI, 95.90-97.43) and false negative rate 4.98%. On logistic regression analysis, micrometastasis (Odds ratio (OR) 7.76, 95% CI, 3.49-17.25, P < .001) lobular histology (OR 2.50, 95% CI, 1.007-6.223, P = .04) and nodes dissected (OR 1.18, 95% CI, 1.07-1.30, P = .001) were associated with higher false negative FS, and extra nodal extension (OR 0.32, 95% CI, 0.18-0.57, P ≤ .001) with lower false negative FS. CONCLUSION: The high concordance between intraoperative FS and definitive histology, suggests it's routine use for Sentinel lymph node/LAS LN can help avoid a second surgery.

Computational pathology improves risk stratification of a multi-gene assay for early stage ER+ breast cancer.

Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN- IBC. H&E images from a total of n = 321 patients with ER+ and LN- IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02-5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18-7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20-89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone.

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.

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.

Effect of Peritumoral Infiltration of Local Anesthetic Before Surgery on Survival in Early Breast Cancer.

PURPOSE: Preventing metastases by using perioperative interventions has not been adequately explored. Local anesthesia blocks voltage-gated sodium channels and thereby prevents activation of prometastatic pathways. We conducted an open-label, multicenter randomized trial to test the impact of presurgical, peritumoral infiltration of local anesthesia on disease-free survival (DFS). METHODS: Women with early breast cancer planned for upfront surgery without prior neoadjuvant treatment were randomly assigned to receive peritumoral injection of 0.5% lidocaine, 7-10 minutes before surgery (local anesthetics [LA] arm) or surgery without lidocaine (no LA arm). Random assignment was stratified by menopausal status, tumor size, and center. Participants received standard postoperative adjuvant treatment. Primary and secondary end points were DFS and overall survival (OS), respectively. RESULTS: Excluding eligibility violations, 1,583 of 1,600 randomly assigned patients were included in this analysis (LA, 796; no LA, 804). At a median follow-up of 68 months, there were 255 DFS events (LA, 109; no LA, 146) and 189 deaths (LA, 79; no LA, 110). In LA and no LA arms, 5-year DFS rates were 86.6% and 82.6% (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95; P = .017) and 5-year OS rates were 90.1% and 86.4%, respectively (HR, 0.71; 95% CI, 0.53 to 0.94; P = .019). The impact of LA was similar in subgroups defined by menopausal status, tumor size, nodal metastases, and hormone receptor and human epidermal growth factor receptor 2 status. Using competing risk analyses, in LA and no LA arms, 5-year cumulative incidence rates of locoregional recurrence were 3.4% and 4.5% (HR, 0.68; 95% CI, 0.41 to 1.11), and distant recurrence rates were 8.5% and 11.6%, respectively (HR, 0.73; 95% CI, 0.53 to 0.99). There were no adverse events because of lidocaine injection. CONCLUSION: Peritumoral injection of lidocaine before breast cancer surgery significantly increases DFS and OS. Altering events at the time of surgery can prevent metastases in early breast cancer (CTRI/2014/11/005228).[Media: see text].

Determinants of pathological complete response to neoadjuvant chemotherapy in breast cancer: A single-institution experience.

Background: Neoadjuvant chemotherapy (NACT) is routinely used in all cases of locally advanced breast cancer and some cases of early breast cancer. We previously reported a pathological complete response (pCR) rate of 8.3%. With the increasing use of taxanes and human epidermal growth factor receptor 2 (HER2)-directed NACT, we conducted this study to understand the current pCR rate and its determinants. Methods: A prospective database of breast cancer patients who underwent NACT followed by surgery between January and December 2017 was evaluated. Results: Of the 664 patients, 87.7% were cT3/T4, 91.6% were grade III, and 89.8% were node-positive at presentation (54.4% cN1, 35.4% cN2). The median age was 47 years; median pre-NACT clinical tumor size was 5.5 cm. Molecular subclassification was 30.3% hormone receptor positive (HR+) HER2-, 18.4% HR+HER2+, 14.9% HR-HER2+, and 31.6% triple negative (TN). Both anthracyclines and taxanes were given preoperatively in 31.2% patients whereas 58.5% of HER2 positive patients received HER2-targeted NACT. The overall pCR rate was 22.4% (149/664), 9.3% in HR+HER2-, 15.6% in HR+HER2+, 35.4% in HR-HER2+, and 33.4% in TN. On univariate analysis, duration of NACT (P < 0.001), cN stage at presentation (P = 0.022), HR status (P < 0.001), and lymphovascular invasion (P < 0.001) were associated with pCR. On logistic regression, HR negative status (Odds ratio [OR] 3.314, P < 0.001), longer duration of NACT (OR 2.332, P < 0.001), cN2 stage (OR 0.57, P = 0.012), and HER2 negativity (OR 1.583, P = 0.034) were significantly associated with pCR. Conclusion: Response to chemotherapy depends on molecular subtype and duration of NACT. A low rate of pCR in the HR+ subgroup of patients warrants reconsideration of neoadjuvant strategies.

Synchronous and Metachronous Breast and Ovarian Cancers: Experience from a Single Tertiary Care Cancer Centre in India.

Women with either breast cancer (BC) or ovarian cancer (OC) have a 1.5-2 times higher risk of developing the other. Discerning discrete primaries versus metastases from either can be challenging. Clinico-pathological and outcome details of patients diagnosed with both BC and OC from December 1994 to August 2018 were retrospectively evaluated at a single tertiary cancer centre. We report the pattern of presentation and recurrences with case-based illustrations. Out of 139 patients, presentation was BC-first in 66.2%, OC-first in 24.5% and synchronous cancers (SC) in 9.3% of women. The median age at diagnosis in BC-first, OC-first and SC was 42 years, 48 years and 49 years, respectively. The most common histological subtype was invasive breast carcinoma-no special type (74.8%) in BC and serous cystadenocarcinoma (81.3%) in OC. BC presented at an early stage in 67.6% while OC presented at an advanced stage in 48.2% of patients. Germline mutation results were available in 82% with 61.4% of the cohort exhibiting a mutation- BRCA1 mutation being the most common. The median time to development of second cancer was 77.4 months and 39.4 months in BC-first and OC-first, respectively. At a median follow-up of 9.47 years, disease-free survival was 32.6%, 32.4% and 30.8% in BC-first, OC-first and SC, respectively (p < 0.001). In hereditary breast and ovarian cancer, BC-first patients have a better prognosis while synchronous malignancies have worse oncological outcomes. Deaths are mainly due to OC progression. Appropriate surveillance and prophylactic intervention in young patients with breast cancer may improve overall outcomes.

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.

Access to HER2-targeted therapy at a tertiary care center in India: An evolution.

Background: In a previous retrospective audit from our institution we reported that patients had limited access to HER2-targeted therapy due to financial constraints. Subsequently, the advent of biosimilar versions of trastuzumab and philanthropic support has potentially changed this situation. Herein, we reanalyzed and reported access to HER2-targeted therapy in a more recent cohort of patients. Methods: Medical records of new breast cancer patients registered in one calendar year were retrospectively reviewed, supplemented by online pharmacy data to extract information on receptor status, use of HER2-targeted therapy, and other relevant variables. Since not all HER2 immunohistochemistry (IHC) 2+ tumors underwent fluorescent in-situ hybridization (FISH) testing, we estimated the probable HER2 amplified from this group based on a FISH amplified fraction in those HER2 2+ tumors who did undergo FISH. Results: Between January 2016 and December 2016, 4717 new BC patients were registered at our institution, of whom 729 (20.04%) had HER2 IHC 3+ tumors while 641 (17.62%) had HER2 IHC 2+ tumors. The final number of HER2 overexpressing/amplified tumors was estimated to be 928 (729 HER2 IHC 3+, 105 known FISH amplified, and 94 estimated FISH amplified), of whom 831 received treatment at our institution. Overall 474 (57.03%, 95% confidence interval [CI] 53.6-60.4) of these 831 patients received trastuzumab for durations ranging from 12 weeks to 12 months in the (neo)adjuvant setting or other durations in metastatic setting compared to 8.61% (95% CI 6.2-11.6) usage of HER2-targeted therapy in the 2008 cohort. Conclusion: Access to HER2-targeted therapy has substantially increased among patients treated at a public hospital in the past decade, likely due to the advent of biosimilars, the use of shorter duration adjuvant regimens, and philanthropic support. However, further efforts are required to achieve universal access to this potentially life-saving treatment.

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.