Indian Breast Cancer Research Articles

DEMOGRAPHIC, CLINICO-PATHOLOGICAL PROFILE, AND IMMUNOHISTOCHEMISTRY STUDY IN FEMALE BREAST CANCER IN EASTERN INDIA: A HOSPITAL-BASED RETROSPECTIVE STUDY

Objectives: Female breast cancer is the most common cancer in Worldwide. In India, locally advanced female breast cancer is more common (57%) and survival rate of female breast cancer is very poor because early age of disease onset, diagnosed in late stage, delayed initiation, and inadequate proper treatment. Few studies have been published in journals regarding clinico-pathological profile of breast cancer in India. However, there are limited data available in literature on demographic, clinico-pathological profile, and immunohistochemistry (IHC) study in female breast cancer in Eastern India. Methods: Newly diagnosed, histopathology proved female breast cancer patients registered from January 2018 to June 2022 at department of radiotherapy was included in this study. This study was retrospective and primary data were collected from medical records of patients about their demographic, clinico-pathological, and IHC profile. Results: The median age at diagnosis was 48 years. Incidence of female breast cancer was more in the age group of 41–50 years (39.5%) and most of the patients were in premenopausal group (59.2%). Locally advance disease, Stage III (50.7%) was more followed by Stage II (32.2%). Most common histopathology type was invasive ductal carcinoma not otherwise specified (90.8%) and Grade II (50%). Triple negative breast tumor was more common IHC type (32.9%). Conclusions: In our study, locally advanced breast cancer was more common in premenopausal patients in urban area. Awareness regarding breast cancer among general population, early diagnosis and adequate proper treatment can reduce mortality of breast cancer.

463P Cost effectiveness of palbociclib and ribociclib in metastatic breast cancer in India using ICER and QALY

Cyclin dependent kinase inhibitors (CDK 4/6) are the mainstay of treatment in metastatic Hormone receptor positive (HR+) HER-2 negative breast cancer, having impressive Progression free survival (PFS) and overall survival (OS) results. The approved agents are Palbociclib, Ribociclib and Abemaciclib. OS data are not yet mature for Abemaciclib. Cost effectiveness of these drugs has not been studied in the Indian context, where most patients resort to out of pocket expenditure (OOP). This study was undertaken to analyse the cost effectiveness of Palbociclib and Ribociclib by calculating the quality adjusted life years (QALY) and Incremental cost effective ratio (ICER).

20P Physician perceptions to use of trastuzumab in HER2+ breast cancer in India

Biosimilars have the potential for cost savings and thus help increase access to treatment. The study aims to understand the physicians’ perception and usage of biosimilars in HER2+ breast cancer (BC) and changes in trends from pre-biosimilar (only innovator trastuzumab was available) to current biosimilar era in India.

104 (PB-104) Poster - Comprehensive mutation profiling of PIK3CA gene in Indian breast cancer patients

Background: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer-related death among women worldwide. It is a complex, heterogeneous disease in which several lifestyle-related and genetic factors are implicated in its pathogenesis. The phosphatidylinositol 3-kinase (PI3 K) is a complex signaling pathway that plays an essential role in cell growth, proliferation, epithelial to mesenchymal transition, survival, invasion, migration, and apoptosis. It is often altered in BC caused by mutations or amplification of the genes encoding the PI3 K catalytic subunits p110α (PIK3CA).

Transcriptomic profiling of Indian breast cancer patients revealed subtype-specific mRNA and lncRNA signatures.

Breast cancer (BC) is one of the leading causes of cancer-associated death in women. Despite the progress in therapeutic regimen, resistance and recurrence of breast cancer have affected the overall survival of patients. The present signatures, such as PAM50 and Oncotype DX, do not segregate the Indian breast samples based on molecular subtypes. This study aims at finding signatures of long noncoding RNA (lncRNA) and mRNA in Indian breast cancer patients using RNA-seq. We have analyzed the survival based on the menopausal and hormone status of 380 Indian breast cancer patients, and of these, we have sequenced and analyzed matched tumor-normal transcriptome of 17 (pre- and postmenopausal) Indian breast cancer patients representing six different subtypes, namely, four patients in triple-positive, three patients in estrogen receptor-positive (ER+ve), three patients in estrogen and progesterone receptors-positive (ER+ve, PR+ve), two patients in human epidermal growth factor receptor (Her2+ve), three patients in triple-negative, and one patient in ER+ve and Her2+ve subtypes. We have identified a 25 mRNA-27 lncRNA gene set, which segregated the subtypes in our data. A pathway analysis of the differentially expressed genes revealed downregulated ECM interaction and upregulated immune regulation, cell cycle, DNA damage response and repair, and telomere elongation in premenopausal women. Postmenopausal women showed downregulated metabolism, innate immune system, upregulated translation, sumoylation, and AKT2 activation. A Kaplan-Meier survival analysis revealed that menopausal status, grade of the tumor, and hormonal status displayed statistically significant effects (p < 0.05) on the risk of mortality due to breast cancer. Her2+ve patients showed low overall survival. One of the unique lncRNA-mRNA pairs specific to the EP-subtype, SNHG12 and EPB41, showed interaction, which correlates with their expression level; SNHG12 is downregulated and EPB41 is upregulated in EP samples.

Clinicopathologic Correlation of CD44 + /CD24 - Expression in Breast Cancer: a Report from Tertiary Care Medical University in India.

CD44 + /CD24 - phenotype has been associated with stem cell-like characteristics with enhanced invasive properties, radiation resistance, and with distinct genetic profiles suggesting a correlation to adverse prognosis in western literature. The aim of this study was to study CD44 + /CD24 - phenotype as an adverse prognostic marker in Indian breast cancer patients. N = 61 breast cancer patients included in a tertiary care facility in India were evaluated for receptor studies (estrogen receptor ER, progesterone receptor PR, Herceptin antibody Her2 neu receptor, CD44 & CD24 stem cell markers). CD44 + /CD24 - phenotype was statistically related to adverse factors like estrogen and progesterone receptors non-expression, her 2 neu expression, and triple-negative breast cancer. Of the 39 patients with ER-ve status, 33 (84.6%) were found to have CD44 + /CD24 - phenotype and 82.5% of all the CD 44 + /CD24 - patients were ER negative (p = 0.001). Thirty-four (75.5%) of the PR-ve patients showed the CD44 + /CD24 - phenotype, and of all the CD 44 + /CD24 - patients, 85% of were PR negative (p = 0.006). Thirty-six (75%) of Her-2-Neu + ve were CD44 + /CD24 - . Approximately 90% of the Her 2 Neu patients expressed CD44 + /CD24 - and 76.9% of all the triple-negative patients were found to be CD44 + /CD24 - expression (p = 0.001). CD44 + /CD24 - had a significant association with adverse prognostic factors like stage of disease, hormonal receptor status, and molecular subtypes in Indian breast cancer patients like the Western data.

Cost-effectiveness of Post-Mastectomy Radiotherapy (PMRT) for breast cancer in India: An economic modelling study.

The role of post-mastectomy radiotherapy (PMRT) for breast cancer is controversial when 3-or-less lymph nodes are metastatic. Apart from local control, survival and toxicity, cost also plays an important role in decision-making. A Markov model was designed to assess cost, health outcomes and cost-effectiveness of different radiotherapy techniques for management of PMRT patients. Thirty-nine scenarios were modelled based on type of radiotherapy, laterality, pathologic nodal burden, and dose fractionation. We considered a societal perspective, lifetime horizon and a 3% discount rate. The data on quality of life (QoL) was derived using the cancer database on cost and QoL. Published data on cost of services delivered in India were used. Post-mastectomy radiotherapy results in incremental quality adjusted life years (QALYs) that ranged from -0.1 to 0.38 across different scenarios. The change in cost ranged from estimated median savings of USD 62 (95% confidence intervals: -168 to -47) to incurring an incremental cost of USD 728 (650-811) across different levels of nodal burden, breast laterality and dose fractionation. For women with node-negative disease, disease-specific systemic therapy remains to be the preferred strategy. For women with node-positive disease, two-dimensional radiotherapy (2DRT) with hypofractionation is the most cost-effective strategy. However, a CT based planning is preferred when maximum heart distance (MHD) >1cm, irregular chest wall contour and inter-field separation >18cm. PMRT is cost-effective for all node-positive patients. With similar toxicity and effectiveness profile compared with conventional fractionation, moderate hypofractionation significantly reduces the cost of treatment and should be the standard of care. Conventional techniques for PMRT are cost-effective over newer modalities which provide minimal additional benefit, at high cost. The funding to collect primary data for study was provided by Department of Health Research, Ministry of Health and Family Welfare, New Delhi, wide letter number F. No. T.11011/02/2017-HR/3100291.

Prevalence, Characteristics, and Correlates of Fatigue in Indian Breast Cancer Survivors: A Cross-Sectional Study.

Navneet KaurBackground Fatigue is one of the commonest sequelae of breast cancer treatment that adversely impacts quality of life (QOL) of breast cancer survivors (BCSs). However, very limited data are available about cancer-related fatigue in Indian patients. Hence, this study was planned with the objectives to study (1) prevalence of fatigue in short-, intermediate-, and long-term follow-up; (2) severity and characteristics of fatigue; (3) impact of fatigue on QOL; and (4) correlation of fatigue with other survivorship issues. Materials and Methods The study was conducted on ( n = 230) BCSs who had completed their primary treatment (surgery, radiotherapy, and chemotherapy) and were coming for follow-up. The prevalence of fatigue was noted from a screening tool, which comprised of 14 commonly reported survivorship issues. Assessment of fatigue was done by using survivorship fatigue assessment tool-1 score and QOL was assessed by functional assessment of cancer therapy-breast (FACT-B) questionnaires. To understand how fatigue evolved over time, survivors were divided into three groups according to the time elapsed since initial treatment: Group 1: <2 years ( n = 105); Group 2: 2-5 years ( n = 70); Group 3: >5 years ( n = 55). Statistical Analysis Data was analyzed by using simple descriptive statistics, one way analysis of variance followed by Tukey's test for comparison of quantitative data among the three groups, and Pearson correlation coefficients for association of fatigue with other survivorship issues. Results Clinically significant fatigue (≥4) was noted in 38% of BCSs. However, high overall prevalence of fatigue (60%) was seen, which persisted in long-term survivors (51%) as well. Severity of fatigue was mostly mild (37.7%) to moderate (47.1%). Fatigue scores were significantly higher in short-term survivors ( 5.01 ± 2.06) than intermediate- (4.03 ± 1.42) and long-term BCSs (3.57 ± 1.37). The mean score on FACT-B was 90.07 ± 10.17 in survivors with fatigue and 104.73 ± 7.13 in those without fatigue ( p = 0.000). Significant correlation of fatigue was seen with other survivorship issues like limb swelling, chronic pain, premature menopause, and its related symptoms and emotional distress. Conclusion Fatigue is highly prevalent in BCSs. Survivorship care programs should include appropriate measures to evaluate and address fatigue.

Risk Factors for Breast Cancer

To prevent new cancers from starting, scientists look at risk factors and protective factors. Anything that increases chance of developing cancer is called a cancer risk factor; anything that decreases your chance of developing cancer is called a cancer protective factor. The survival rates of breast cancer in India are low because the detection takes place late. The only way to change these numbers is by increasing awarenessSome risk factors for cancer can be avoided, but many cannot. Avoiding risk factors and increasing protective factors may lower risk for breast cancer.

Quality of Life Post Breast Cancer Surgery: Comparison of Breast Conservation Surgery versus Modified Radical Mastectomy in a Developing Country.

Introduction Breast cancer survivors are the largest group of female cancer survivors. Oncologic breast surgery can have a profound impact on a woman's body image and sense of self that can significantly affect their quality of life (QOL). The paucity of data about the effect of type of surgery on QOL of Indian breast cancer survivors has led to this study. Materials and Methods This prospective study included consecutive female early breast cancer patients who underwent primary surgery, that is, breast conservation surgery (BCS) or modified radical mastectomy (MRM) from January 1, 2015 to December 31, 2015. The primary objective was the comparison of QOL using European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and EORTC QLQ-BR 23 between the two groups at 6 months and 1 year postsurgery with the baseline. Results One hundred and thirty-eight patients were included of which 62 underwent BCS and 76 underwent MRM. BCS patients fared better with respect to physical functioning, dyspnea, fatigue, appetite loss, and body image at 6 months ( p < 0.05) as compared with MRM. At 1 year postsurgery, BCS patients fared better with respect to physical functioning, role functioning, global health status, body image, sexual enjoyment, and dyspnea, while MRM patients fared better in emotional functioning and future prospectives ( p < 0.05). Conclusion Patients undergoing BCS have a better QOL with respect to various functional and symptom scales at 6 months and 1 year. However, patients undergoing MRM perform better in terms of future perspective and emotional functioning at 1 year.

Barriers to Early Diagnosis and Treatment among Breast Cancer Survivors: Qualitative Study in Tertiary Care Hospital, North Karnataka

Introduction: Around the World, Breast cancer has become one of the common cancers among women. Prevalence and mortality of Breast cancer in India are 18 lakh &amp; 12.7 per lakh cases respectively. One of the important reasons behind late presentation &amp; high death rate is the lack of breast cancer awareness.&#x0D; Objectives: To assess the barriers in diagnosis and treatment among breast cancer patients and to explore the perception about cancer prevention among them.&#x0D; Methods: A qualitative study was done among women with confirmed breast cancer who were admitted to KIMS, Hubballi, and Cancer hospital, Navanagar in April 2019. Data collection was done by the In-depth interview method and analyzed as per qualitative study protocol standards.&#x0D; Results: The data was collected among 14 participants. Themes were generated accordingly. The findings showed lack of awareness, myths, financial constraints, negligence were the major barriers to the early presentation of breast cancer.&#x0D; Conclusion: This study showed barriers such as lack of awareness, negligence, fear, financial constraints, myths and misconceptions, social stigma, lack of family support. Measures taken to reduce mortality by early diagnosis and treatment.

Breast cancer in India: Present scenario and the challenges ahead.

Breast cancer is the commonest malignancy among women globally. From being fourth in the list of most common cancers in India during the 1990s, it has now become the first. In this review, we examine the available literature to understand the factors that contributed to the high burden of breast cancer in the country. We also provide the landscape of changes in the field of early diagnosis and the treatment modalities as well as the limitations of the Indian healthcare delivery systems (e.g., delayed diagnosis, human resources and funding for treatment). This review also sheds light on the newer interventions and the future of breast cancer management keeping in mind the coronavirus disease 2019 imposed limitations.

Triple Negative Breast Cancer in India: What Is the Real Incidence?

Triple Negative Breast Cancer in India: What Is the Real Incidence?

FOXO1 Gene Downregulation and Promoter Methylation Exhibits Significant Correlation With Clinical Parameters in Indian Breast Cancer Patients.

Background: Forkhead box “O” one which is member of Forkhead box family of transcription factors is known to play key role in different physiological processes including cell cycle arrest, autophagy, and apoptosis. FOXO1 is defined to play tumor suppressive role in various malignancies including breast cancer and its Dysregulation is frequently reported. However, the evaluation of FOXO1 promoter methylation and its expression at mRNA and protein level in different stages of breast cancer and its association with different clinical parameters is still not studied. Therefore, for better understanding the role of FOXO1 in breast cancer, in our study we examined the FOXO1 mRNA and protein expression in Breast cancer samples of Indian breast cancer patients. Results: Total 127 breast cancer samples along with adjacent normal tissue (n = 127) were analyzed through methylation specific PCR (MS-PCR), mRNA expression (Real-time PCR) and Immunohistochemistry (IHC). We detected 69.29% cases to be downregulated at the mRNA level, and 77.95% of cases exhibited no or low protein expression. In our data we report a significant association (p = 0.0001) between the downregulated protein expression and promoter hypermethylation of FOXO1 gene. We also found a significant correlation of FOXO1 mRNA level with Age (p = 0.008), age at first live birth (p = 0,003), tumor size (p = 0.05) and lymph node status (p = 0.01). Conclusion: we in our study report the tumor suppressive role of FOXO1 in case of Indian breast cancer patients and our data suggest it to exhibit prognostic importance. However, further research is needed to evaluate FOXO1 significance in diagnostic and therapeutic targeting in breast cancer cases.

Determining Vitamin D Status: A Comparison Between Diabetic And Non-diabetic Women With Breast Cancer By RP-HPLC

Suboptimal levels of Vitamin D, remains a common problem worldwide and its prevalence is high in India, ranging from 70-100%. Several molecular mechanisms have been found about the effects of Vitamin D in modulating glycemic levels and its protective nature in the development of breast cancer. Breast cancer in India is a common problem and studies regarding its association with Vitamin D levels among diabetics remain inconclusive. This study aims to find the association between Vitamin D status and breast cancer in diabetic and non-diabetic women.

Abstract P3-07-08: Germline mutational profiling in Indian TNBCs

Abstract Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. The high TNBC prevalence (&amp;gt;25%) in India as compared to the western population (10-15%) remains to be a challenge in clinical management. The association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. However, these studies are predominantly from germline profiling of TNBCs representative of western population. Therefore, we aimed to investigate the germline profiles of Indian breast cancer patients using a multi-institutional TNBC cohort based on ACMG consensus multi-gene NGS panel. In our study cohort of 193 TNBC patients, we identified 57 pathogenic mutations (diagnostic yield = 29.53%) from various genes of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. We observed a high prevalence of BRCA1 mutations (41/193, 21.24%) and BRCA2 mutations (8/193, 4.14%) in our cohort as compared to published literature. Additionally, 8 pathogenic mutations were also reported in non-BRCA cancer pre-disposing genes associated with the HR pathway like ATM, CHEK2, PALB2. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. The most common type of mutations was found to be frame-shift which may cause protein truncation and loss of function. Furthermore, we identified 48 variants of unknown significance (24.9%) of which about 7% were in the BRCA1/2 genes. Data mining from global databases like TCGA, Genome Asia indicated that the novel mutations were unique to the Indian population compared to the germline profiles of different ethnicities. Our study confirms the major contribution of BRCA1/2 genes in TNBCs as reported in the literature. A high percentage of the women were found to be associated with young age onset which may be attributed to BRCA mutations. Further analysis to investigate the association of tumor size, tumor grade, survival analysis with mutational profiles is in process. Similarly, we are also assessing. family history to underline the importance of multi-gene panel testing as recommended by NCCN guidelines. Moreover, our results also emphasize the need for designing/implementing guidelines specific to Indian population. In summary our results indicate that Indian TNBCs have a high prevalence of BRCA1/2 mutations. Large scale studies in future are warranted to validate these preliminary findings. Citation Format: C B Koppiker. Germline mutational profiling in Indian TNBCs [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-07-08.

Practical Consensus Recommendations for Optimizing Risk versus Benefit of Chemotherapy in Patients with HR Positive Her2 Negative Early Breast Cancer in India.

Breast cancer is a public health challenge globally as well as in India. Improving outcome and cure requires appropriate biomarker testing to assign risk and plan treatment. Because it is documented that significant ethnic and geographical variations in biological and genetic features exist worldwide, such biomarkers need to be validated and approved by authorities in the region where these are intended to be used. The use of western guidelines, appropriate for the Caucasian population, can lead to inappropriate overtreatment or undertreatment in Asia and India. A virtual meeting of domain experts discussed the published literature, real-world practical experience, and results of opinion poll involving 185 oncologists treating breast cancer across 58 cities of India. They arrived at a practical consensus recommendation statement to guide community oncologists in the management of hormone positive (HR-positive) Her2-negative early breast cancer (EBC). India has a majority (about 50%) of breast cancer patients who are diagnosed in the premenopausal stage (less than 50 years of age). The only currently available predictive test for HR-positive Her2-negative EBC that has been validated in Indian patients is CanAssist Breast. If this test gives a score indicative of low risk (< 15.5), adjuvant chemotherapy will not increase the chance of metastasis-free survival and should not be given. This is applicable even during the ongoing COVID-19 pandemic.

Epigenetic Alteration and its Association With Downregulated FOXP3 Gene in Indian Breast Cancer Patients.

Background: FOXP3 gene, known to be a potential tumor suppressor, has been identified to interact with HER2 in mammary cancer. Moreover, the high expression of FOXP3 serves as a good predictor of the survival of patients in breast cancer, prostate cancer, and gastric cancer. The expression and epigenetic alterations were evaluated in female breast cancer patients. Material and Methods: Expression studies at the mRNA level and protein level were conducted in 140 breast cancer cases by real-time PCR and immunohistochemistry, respectively. Epigenetic studies were also conducted by analyzing the methylation status at the promoter region of the gene using MS-PCR. Results: FOXP3 mRNA expression and protein expression were downregulated in breast cancer patients. The absence of FOXP3 protein expression is significantly associated with promoter methylation, where 70 methylated cases exhibited protein loss (70/95, 73.6%). Statistically, we also found a significant correlation between FOXP3 protein expression and TNM stage, promoter methylation, and histological grade. The methylated FOXP3 cases that did not express protein were also significantly associated with positive lymph node metastasis and HER-2 status. Conclusion: The expression profile of FOXP3 may serve as a prognostic factor. In short, FOXP3 may stand in the most crucial list of biomarkers for breast cancer, bringing compelling results in terms of treatment and management of the disease.

Association of Breast Surgeons of India (ABSI) Practical Consensus Statement, Recommendations, and Guidelines for the Treatment of Breast Cancer in India 2021—Indian Solutions for Indian Problems

Association of Breast Surgeons of India (ABSI) Practical Consensus Statement, Recommendations, and Guidelines for the Treatment of Breast Cancer in India 2021—Indian Solutions for Indian Problems

Immunohistochemical Markers in Breast Cancer: A Cross-Sectional Study on Triple-Negative Breast Cancer in a Rural Tertiary Care Hospital.

IntroductionThe incidence of breast cancer in India is on the rise, and it is now the most common cancer affecting women in India. The main objective of our study was to estimate the prevalence of triple-negative breast cancer (TNBC) in our study population and compare the various clinicopathological characteristics of TNBC with those of non-TNBC in these patients.MethodsA retrospective, cross-sectional study was conducted among 249 cases of female breast cancer who reported to a tertiary care hospital in Southern India from September 2017 to September 2021.ResultsThe mean age at presentation was 52 years (range: 26-82 years). The prevalence of triple-negative breast cancer was 19.7%. Most of the subjects belonged to the age group of 40-60 years. The majority were with grade 2 and 3 diseases. Of the cases, 50.6% were estrogen receptor (ER) positive and 48.2% were progesterone receptor (PR) positive, and 40.1% were HER2/neu positive.ConclusionThe prevalence of triple-negative breast cancer in our study population is 19.7%, which is in concordance with the literature. Large tumor size, high-grade tumors, and a higher rate of axillary lymph node metastasis are characteristic features of TNBC. TNBC are tumors with aggressive tumor biology and are associated with poor prognosis.