Family History Of Breast Carcinoma Research Articles

Large cohort analysis of incidental CDH1 PVs among patients undergoing MGPT.

10618 Background: Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant condition caused by a heterozygous pathogenic variant (PV) in CDH1.HDGC is associated with an increased risk for DGC (33-70%) and invasive lobular breast cancer (LBC) (~64%) [1]. The National Cancer Center Network (NCCN) and International Gastric Cancer Linkage Consortium (IGCLC) recommend consideration of CDH1 germline testing based on personal and family history of DGC and LBC. However, with the advent of next generation sequencing and the inclusion of CDH1 in multigene panels (MGP), several cohort studies have identified CDH1+ patients who do not meet criteria [2,3,4,5]. Our group previously analyzed a cohort of patients with a personal or family history of BC who had CDH1 testing through MGPT and did not observe a significant association between CDH1 PVs and suspicion for HDGC (p-value=0.2066) [6]. In this expanded study, we aim to evaluate a larger cohort of patients of all cancer histories to gain a more comprehensive picture of the prevalence of incidental CDH1 PV among patients undergoing MGPT. Methods: 14,891 individuals who underwent CDH1 testing within MGPT were seen at MD Anderson’s Clinical Cancer Genetics (CCG) program between August 2013 and January 2024. This cohort was obtained from a prospectively maintained patient database within MD Anderson’s CCG program. Individuals were stratified based on CDH1 germline status (PV vs. negative or variant of uncertain significance) and meeting modified criteria for HDGC. Results: Within our expanded cohort, 1,716 individuals (11.5%) met criteria for suspicion for HDGC, while 13,715 did not meet criteria. Of the 70 individuals who tested positive for CDH1 (0.47%), 39 (0.28%) met criteria while 31 (0.23%) did not. We observed a statistically significant relationship between meeting our modified criteria for suspicion for HDGC and testing positive for a pathogenic variant in CDH1 (p-value <0.0001). Conclusions: Among patients who underwent CDH1 testing within MGPT, we observed a correlationbetween having a CDH1PV and meeting criteria for suspicion for HDGC. This contrasts with prior findings from our breast cancer cohort, potentially due to the limited number of CDH1 positive patients (n=3). These results suggest that while perhaps not robustly capturing HDGC families within a sub-population of patients undergoing MGPT, overall, NCCN and IGCLC guidelines closely reflect the clinical picture of a significant number of HDGC families. Meanwhile, the presence of incidental CDH1 PVs in this cohort portrays the variable expressivity and incomplete penetrance among patients with HDGC, including the detection of occult signet ring cell carcinomas during endoscopies or total gastrectomies [7]. We seek to expand this analysis by comparing these findings to rates of incidental CDH1 PVs in a subset of patients who meet NCCN guidelines for CDH1 testing based on suspicion for hereditary breast cancer syndromes.

Abstract PO1-16-11: Real-world features and outcomes of young advanced breast cancer (ABC) patients (pts) from RegistEM (GEICAM/2014-03) study

Abstract Background: BC is the most incident cancer worldwide in < 40 years old (y) women. Increasing body mass index and changes in reproductive history contribute to the growing incidence of premenopausal BC. A higher proportion of luminal B-like and estrogen receptor negative (ER─) tumors, an increased risk of early relapse, and more unfavorable longer-term outcomes for young women with ER+ tumors when compared to older women, have been reported. In this analysis, we focus on age-specific BC characterization from a real-world population-based perspective. Methods: Pts were enrolled in the non-interventional and ambispective RegistEM study in ABC diagnosed between 2016 and 2019. We describe the features and outcomes of < 50 y pts at their initial BC diagnosis according to their BC subtype. BC subtypes were based on the most recent tumor tissue sample (distant metastasis, and in its absence, primary BC). Comparisons between < 40 and ≥ 50 y groups were performed. Results: Pts < 50 y represent 39% (n=685) of total pts with available data (n=1739, any age group) in the registry. By age, 12% (n=212) were < 40y, and 27% (n=473) 40-49y. At first BC diagnosis, 75% and 25% pts had early BC (EBC) and de novo metastatic BC (MBC), respectively. In EBC pts, stage II (50%) and III (28%) were the most frequent at diagnosis; invasive non-special type carcinoma was the predominant morphology, and grade 2 was the most common histological grade, but grade 3 was predominant in TN pts and HER2+ < 40y pts. The median time to recurrence was < 2y in TN pts, 3y in HER2+ pts, and 6y in luminal HER2─ pts. At ABC diagnosis, the median age was 47y, all pts were female but one, 98% white, and 60% premenopausal (94% were premenopausal at EBC diagnosis). A family history of BC and/or ovarian cancer was reported in 34% pts, and a hereditary-risk genetic test was performed in 39% (254 of 652) pts; 12% (n=30) had BRCA1/2 mutations, with a proportion higher in TN pts (9 of 33, 27%) vs. luminal HER2─ (21 of 183, 12%) and HER2+ (0 of 38) pts. Visceral disease was the most frequent in all subgroups, highlighting statistical differences (p=0.022) between age groups ( < 40y 55% vs. ≥50y 71%) only in TN pts. 60% had ≤ 2 locations involved, similarly in all subgroups. The presence of >2 metastatic locations was statistically higher in HER2+ pts ≥50y (54%) vs both < 40y (32%) and 40-49y (48%). Brain disease was more present at ABC diagnosis in TN (9%) and HER2+ (7%) than in luminal HER2─ (3%). Median no. of treatment lines (L) was 3 (range 0-11), and median follow-up 44 mo (95% CI: 41-44). 99% pts received 1L, the distribution of treatments by BC subtype within each age subgroup was similar; median duration of 1L was 21 months (mo) in luminal HER2─, 17 mo in HER2+, and 5 mo in TN pts. 68% of pts who received 1L, reached 2L. Duration of 2L dropped dramatically: 8 mo in luminal HER2─, 6 mo in HER2+, and 2 mo in TN pts. No differences between ≥50y and the rest of pts were observed in PFS for any treatment line. 49% pts had died at the database cut-off date (05-April-23), with no differences between age groups, but TN pts had the highest death rate (80%). Additional data according to BC subtypes and age groups are in the table. Conclusions: Luminal HER2─ was the predominant BC subtype in all age subgroups. Visceral disease was more prevalent in young TN pts compared to older pts. TNBC pts experienced a shorter median time to recurrence and the highest mortality rate regardless of age, compared to HER2+ and luminal HER2- pts, indicating the need for targeted interventions in this subgroup. Citation Format: Sara López-Tarruella, Angel Guerrero, Isabel Álvarez, Silvia Antolin Novoa, Ariadna Tibau, Josefina Cruz, César A Rodríguez, Purificación Martínez, J. Ignacio Chacón, María Hernández, Mireia Margelí, Encarna Adrover, Catalina Falo, Iria González, Álvaro Rodríguez-Lescure, María Marín, César Gómez, Juan de la Haba-Rodríguez, J. José Illaramendi, Raquel Andrés, Andrea Blasco, Mª José Escudero, Susana Bezares, Federico Rojo. Real-world features and outcomes of young advanced breast cancer (ABC) patients (pts) from RegistEM (GEICAM/2014-03) study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-11.

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype

Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation. To evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers' tumor samples, and the association of genetic profiles with clinical-pathological data and survival. This single-center, longitudinal, prospective cohort study was conducted from January 1, 1997, to December 31, 2021, with follow-up until January 31, 2023. Women with LBC seen at the European Institute of Oncology were included. Testing for germline CDH1, BRCA1, and BRCA2 genes was performed. Somatic profiling was assessed for germline CDH1 carriers. Accurate estimates of prevalence of germline CDH1 variants among patients with HLBC and the association of somatic sequence alteration with HLBC syndrome. The Kaplan-Meier method and a multivariable Cox proportional hazards regression model were applied for overall and disease-free survival analysis. Of 5429 cases of primary LBC, familial LBC phenotype accounted for 1867 (34.4%). A total of 394 women with LBC were tested, among whom 15 germline CDH1 variants in 15 unrelated families were identified. Among these variants, 6 (40.0%) were P/LP, with an overall frequency of 1.5% (6 of 394). Of the 6 probands with P/LP CDH1 LBC, 5 (83.3%) had a positive family history of BC and only 1 (16.7%) had sporadic juvenile early-onset LBC. No germline BRCA1 and BRCA2 variants were identified in CDH1 carriers. An inactivating CDH1 mechanism (second hit) was identified in 4 of 6 explored matched tumor samples (66.7%) in P/LP germline carriers. The P/LP CDH1 LBC variant carriers had a significantly lower age at diagnosis compared with the group carrying CDH1 variants of unknown significance or likely benign (42.5 [IQR, 38.3-43.0] vs 51.0 [IQR, 45.0-53.0] years; P = .03). In this cohort study, P/LP germline CDH1 variants were identified in individuals not fulfilling the classic clinical criteria for HDGC screening, suggesting that identification of these variants may provide a novel method to test women with LBC with early age at diagnosis and/or positive family history of BC.

The risk-based breast screening (RIBBS) study protocol: a personalized screening model for young women.

The optimal mammography screening strategy for women aged 45-49years is a matter of debate. We present the RIBBS study protocol, a quasi-experimental, prospective, population-based study comparing a risk- and breast density-stratified screening model (interventional cohort) with annual digital mammography (DM) screening (observational control cohort) in a real-world setting. The interventional cohort consists of 10,269 women aged 45years enrolled between 2020 and 2021 from two provinces of the Veneto Region(northen Italy). At baseline, participants underwent two-view digital breast tomosynthesis (DBT) and completed the Tyrer-Cuzick risk prediction model. Volumetric breast density (VBD) was calculated from DBT and the lifetime risk (LTR) was estimated by including VBD among the risk factors. Based on VBD and LTR, women were classified into five subgroups with specific screening protocols for subsequent screening rounds: (1) LTR ≤ 17% and nondense breast: biennial DBT; (2) LTR ≤ 17% and dense breast: biennial DBT and ultrasound; (3) LTR 17-30% or LTR > 30% without family history of BC, and nondense breast: annual DBT; (4) LTR 17-30% or > 30% without family history of BC, and dense breast: annual DBT and ultrasound; and (5) LTR > 30% and family history of BC: annual DBT and breast MRI. The interventional cohort is still ongoing. An observational, nonequivalent control cohort of 43,000 women aged 45years participating in an annual DM screening programme was recruited in three provinces of the neighbouring Emilia-Romagna Region. Cumulative incidence rates of advanced BC at three, five, and ten years between the two cohorts will be compared, adjusting for the incidence difference at baseline.Trial registration This study is registered on Clinicaltrials.gov (NCT05675085).

Abstract B001: Does deep intronic splicing in breast cancer susceptibility genes contribute to breast cancer?

Abstract Breast cancer (BC) is the most common cancer and leading cause of cancer mortality in women. Average lifetime BC risk for a woman in the United States is 13%. However, pathogenic variants in BC susceptibility genes such as BRCA1/2, ATM, and RAD51C, or high polygenic risk scores substantially increase BC risk. Women with a family history of BC and/or ovarian cancer, BC < age 40, or BC and second primary tumor are considered high-risk with an increased likelihood of having a pathogenic variant in a BC susceptibility gene. Yet, more than 60% of women with high-risk BC test negative for coding variants. In these women, possible causal variation could be non-coding in deep intronic or regulatory regions, or cryptic structural variants (SV). To determine whether deep intronic splicing contributes to BC in high-risk women testing negative for pathogenic coding variants in BC genes, we analyzed the intronic sequences of 649 BRCA1/BRCA2 negative individuals with high-risk BC. The samples had undergone targeted capture sequencing of exons and introns of more than 100 target genes including ATM and RAD51C. From the 649 samples, we identified three intronic splicing variants in ATM and RAD51C in 10 samples (1.5%) that had SpliceAI delta scores >0.5 suggesting changes to splicing. One splicing donor gain variant, RAD51C c.145+246A>T, was found exclusively in women of self-reported African ancestry at a frequency of 0.047. In gnomAD, the variant was found exclusively in individuals of African ancestry at a frequency of 0.012. A 1.3-fold enrichment in variant frequency was observed in AFR women under 65 with breast cancer compared to age-matched cancer free controls in the All of Us dataset. Using lymphoblastoid-cell derived RNA from carriers of RAD51C c.145+246A>T, we performed RT-PCR and cDNA amplification targeting the exons surrounding the variant and observed a lengthened exon. Targeted amplicon sequencing also confirmed the presence of intronic sequence in the variant cDNA. The introduced intronic sequence contains a UGA stop codon 12 bp from the end of the exon which could led to loss of RAD51C function. We have created minigene vectors in the RHCglo background and are performing minigene splicing assays to validate the splicing changes in ATM due to intronic variants. Gene functional assays and association studies will be conducted to determine the functional effects and risk conferred by these variants. Understanding the level of contribution of deep intronic splicing in known BC susceptibility genes is critically important, as results impact sequencing offered to patients, and if positive, their medical management. Citation Format: Mwangala P. Akamandisa, Bradley Wubbenhorst, Kurt D'Andrea, Heather Symecko, Rhonda Gillette, Payal D. Shah, Angela R. Bradbury, Kara N. Maxwell, Susan M. Domchek, Katherine L. Nathanson. Does deep intronic splicing in breast cancer susceptibility genes contribute to breast cancer? [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B001.

Knowledge, attitudes, and practices related to breast cancer screening among female Jordanian university employees: A cross-sectional study

IntroductionTo improve participation in breast screening programs, the level of knowledge about BC, attitudes, and practices of women in different sections of society must be understood. This study aimed to measure the level of knowledge of BC risk factors, signs and symptoms and determine current mammography practices among female employees at Jordanian universities. MethodsA cross-sectional descriptive study was conducted on female employees at Jordanian government universities. Data was collected using a structured questionnaire that included: sociodemographic characteristics, knowledge of BC risk factors, knowledge of BC symptoms and knowledge, attitude and practice of mammography as an early detection method. ResultsA total of 362 participants completed the questionnaire. Overall, 174 scored ≥50% correct answers regarding BC risk factors, while 231 scored ≥50% correct answers regarding BC signs and symptoms. Half of the participants (n = 184, 50.8%) understood mammography to be an early BC detection method. Among those participants, 95 (51.6%) were eligible for screening and 39 (21.2%) had had a previous mammogram. The main reason for not engaging in mammography was the absence of BC signs and symptoms (37.2%). Profession, educational level and family history of BC were associated with increased knowledge of BC risk factors, signs and symptoms (p = 0.01). Lecturers in medical faculties exhibited the highest level of knowledge about mammography compared to participants in other professions (p = 0.02). ConclusionOnly 79 participants had good to excellent knowledge about BC. Participants’ profession was the major indicator for awareness of BC and mammography as an early detection method. Implications for practiceThe findings of this study reinforce the importance of providing BC educational programs for university employees in Jordan to increase awareness of BC and mammography.

Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.

Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem. This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors. This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6 months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92 years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60 years and older were negatively associated with CBC. This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.

Analysis of Breast Cancer Family History, Estrogen Receptor Status, and Breast Cancer Outcomes in Sweden

ImportanceBreast cancer (BC), the most prevalent cancer among women globally, is a heterogeneous disease, with prognosis differing by estrogen receptor (ER) status. Having a family history of BC increases the risk of BC; however, it is unclear whether family history is associated with the prognosis of overall and ER-specific BC.ObjectiveTo assess whether a family history of BC is associated with the prognosis of overall and ER-specific BC.Design, Setting, and ParticipantsThis cohort study was based on data from several national registers in Sweden. All female residents of Stockholm who were born after 1932; had their first BC diagnosis between January 1, 1991, and December 31, 2019; and had at least 1 identified female first-degree relative (FDR) were included. Women who were diagnosed with other types of cancer before their BC diagnosis, were older than 75 years at diagnosis, or had distant metastasis at diagnosis were excluded. A total of 28 649 women were included. Data were analyzed from January 10, 2022, to December 20, 2022.ExposuresFamily history of BC, defined as 1 or more female FDRs diagnosed with BC.Main Outcomes and MeasuresPatients were followed up until BC-specific death, censoring, or end of follow-up on December 31, 2019. The role of family history in BC-specific mortality was investigated using flexible parametric survival models among the full cohort, ER-positive subgroup, and ER-negative subgroup, adjusting for demographic characteristics, tumor characteristics, and treatments received.ResultsAmong 28 649 patients, the mean (SD) age at BC diagnosis was 55.7 (10.4) years; 19 545 (68.2%) had ER-positive BC, and 4078 (14.2%) had ER-negative BC. Overall, 5081 patients (17.7%) had at least 1 female FDR diagnosed with BC, while 384 (1.3%) had a family history of early-onset BC (FDR diagnosed before age 40 years). During the follow-up period (median [IQR], 8.7 [4.1-15.1] years), 2748 patients (9.6%) died of BC. Multivariable analyses revealed that having a family history of BC was associated with a lower risk of BC-specific death among the full cohort (hazard ratio [HR], 0.78; 95% CI, 0.65-0.95) and the ER-negative subgroup (HR, 0.57; 95% CI, 0.40-0.82) in the first 5 years, after which no association was observed. However, having an early-onset family history was associated with a higher risk of BC-specific death (HR, 1.41; 95% CI, 1.03-2.34).Conclusions and RelevanceIn this study, patients with a family history of BC did not necessarily have a worse prognosis. Those with ER-negative status and a family history of BC had more favorable outcomes in the first 5 years after diagnosis, possibly due to enhanced motivation to receive and adhere to treatment. However, patients with a family history of early-onset BC had worse survival, suggesting that genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research.

Pattern of bone metastasis; Central VS. Peripheral skeleton in metastatic breast carcinoma.

Objective: To see the pattern of bone involvement in metastatic breast carcinoma. To study the distribution of bone metastasis, central skeleton vs. peripheral skeleton, in metastatic breast carcinoma. Study Design: Retrospective study. Setting: Department of Surgery, Nishtar Medical University, Multan, in accordance with Breast Clinic MINAR. Period: March, 2021 to August, 2022. Material & Methods: The study was done in breast clinic MINAR, Multan. It was retrospective, non-randomized and single institution based study. The female patients who presented with breast carcinoma from March 2021 to August 2022, aged 25 to 70 years were scrutinized. Among these, the patients with metastatic breast carcinoma having metastasis in bones, confirmed on bone scan, were included in the study. 90 cases were collected in this research. The tumours which primarily arise from bone, lymphoid tumours, soft tissue tumours and bone marrow tumours and bone metastasis due to malignancies arising from other visceral organs were excluded. All the data was entered and analyzed using computer programme SPSS version 25.0. Results: The highest range of patients were between ages of 46-65 years. 87.8% were married, 2.2% were unmarried and 10% were divorced or widow. 43.3% were from rural area and 56.7% were from urban area. 93.3% previously had not any history of breast carcinoma. Only 6.7% had family history of breast carcinoma. 64.4% had menarche during the age of 12 to 14 years. And 42.2% had menopause between 50 to 55 years. While in all these cases 46.7% were those who had no menopause at all when they presented with metastatic breast carcinoma. Among these 13.3% had solitary bone metastasis and 86.7% had metastasis to multiple bones. 46.7 % had central or axial skeletal involvement, 13.3% had peripheral skeletal involvement and 40% had both, including central and peripheral skeleton. Conclusion: This study has shown that among all the patients there were 46.7% patients had central skeletal involvement and 13.3% had peripheral skeleton involvement and 40% had both.

Fibromatosis of the breast; another diagnosis of cancer like lesions: About 4 cases reports

Introduction and importanceDesmoid fibromatosis is a benign monoclonal fibroblastic tumor that was first reported in 1832 and arises from musculoaponeurotic structures. It is an uncommon tumor that can mimic breast carcinoma in both hits clinical and radiological presentation.This entity mainly affects patients in their fourth and fifth decades of life. Case presentationOur four patients were of young women in their 2nd and 3rd decade that consulted for masses of the breast.These lesions were suspicious for malignancy in both their clinical and radiological features despite not having any family history of breast carcinoma. Clinical discussionOnly histology provides the diagnosis, it is locally invasive, non-metastatic but with a high potential of recurrence and the sole treatment is complete and wide local excision with clear margins. ConclusionAlthough it is a rare clinical scenario, the presence of an unusual breast or chest wall tumor such as a desmoid tumor should be considered when obvious breast changes and history do not correlate with routine diagnostic measures.

Abstract P4-07-45: Treatment strategies for advanced triple negative breast cancer patients as per routine clinical practice: analysis from the observational study GEICAM/2014-03 (RegistEM)

Abstract Background: Triple negative breast cancer (TNBC) is well known for its more aggressive course and poorer prognosis compared to other BC subtypes. RegistEM study provides real world data to understand the distribution of BC subtypes in the advanced setting, being its primary objective. Biological samples collection is part of its procedures. This is a non-interventional cohort study and 1,907 patients (pts) have been enrolled up to now (females and males) with advanced BC (ABC), diagnosed from Jan-2016 to Dec-2019, either after recurrence or as first BC diagnosis, in 38 Spanish sites. These pts will be followed for at least 5 years. Methods: In the current analysis (cut-off date 08/April/2022, database ongoing), we describe characteristics, treatment patterns and outcomes, including comparison between recurrent and de novo disease, of 157 pts with advanced TNBC included in the RegistEM study. Those pts represent the 10% of pts available in the database at the cut-off date and with ABC diagnosis up to December 2018 (n=1559). The BC clinical subtypes were histologically confirmed on the most recent tumor lesion (metastatic [M] or primary BC) before starting with the 1st-line therapy. Results: At first ABC diagnosis, 73% pts had recurrent early BC (EBC), 26% de novo MBC and 1% unresectable locally ABC (ULABC). Median age was 57 years (range 30-88), all pts were women, 98% Caucasian and 65% postmenopausal. Family history of BC and/or ovarian cancer was reported in 37% pts, and a hereditary-risk genetic test was performed in 59 of 147 pts. Germline BRCA1/2 and TP53 were the most frequently mutated genes, 21% (6/28) and 47% (8/17) pts, respectively. Visceral involvement was present in 69% pts (similar between recurrent EBC and de novo ABC, although brain metastases were only present in the recurrent EBC group), and ≤ 2 metastatic locations in 59%. In 61% (70/115) pts with recurrent EBC, the subtype was assessed in metastatic lesions, and 39 pts of them also had TN subtype in primary BC. In terms of the most frequent therapies by line: 1) 1st-line: chemotherapy (CT) (60%) and CT/biological therapy (BT) (39%). Of the 87 pts with CT alone, monotherapy was the preferred option in 57% pts (capecitabine 25%, taxanes 16%, and eribulin or vinorelbine, 5% each). Bevacizumab was the most frequent BT (79%) combined with CT (single agent in 56% pts, mostly taxanes and capecitabine). Progressive disease (PD) was reported in 85% pts (similar in pts with both recurrent and de novo MBC or ULABC); 2) 2nd-line: CT (79%) (monotherapy capecitabine, eribulin, taxanes) and CT/BT (17%) (CT-containing bevacizumab 82%). Progression was reported in 92% pts; 3) 3rd-line: CT (90%) (eribulin 33%, platinum-based 25%) and CT/BT (9%) (CT-containing bevacizumab 67%). Progression was reported in 88% pts. At database cut-off date, death was reported in 133 (85%) pts, mainly because of PD. Overall survival (OS) was similar between both groups, recurrent and de novo MBC. Conclusion: In this population of Spanish TNBC pts with ABC, three quarters had recurrent disease. De novo ABC pts had a higher proportion of non-visceral metastases, with absence of brain involvement at the first diagnosis. Single-agent CT and CT plus bevacizumab were the most frequent therapies, and OS was similar between recurrent and de novo MBC pts, although numerically higher in the later group. Citation Format: Silvia Antolin Novoa, César A Rodríguez, Josefina Cruz, Sara López-Tarruella, Ariadna Tibau, Encarna Adrover, Ana Miguel, Mireia Margelí, Purificación Martínez, María Hernández, Antonio Antón, Álvaro Rodríguez-Lescure, Catalina Falo, Isabel Álvarez, Diego Malón, Raquel Andrés, José L Alonso-Romero, César Gómez, J. José Illaramendi, Ruth Campo, Juan José Miralles, Susana Bezares, Federico Rojo, Angel Guerrero-Zotano. Treatment strategies for advanced triple negative breast cancer patients as per routine clinical practice: analysis from the observational study GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-45.

Abstract P3-05-58: Frequency and prognosis of HER2-low status in Mexican patients with metastatic breast cancer

Abstract Background Breast cancer (BC) is the leading cause of cancer and cancer-related death in Mexican women. Recently, low expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification, has gained increased attention as a promising new predictive biomarker for treatment with antibody-drug conjugates, such as trastuzumab-deruxtecan, not currently available in Mexico. To date, the frequency and prognostic value of HER2-low status in the Mexican population with metastatic BC remains unknown. Methods Single center retrospective cohort of patients diagnosed with metastatic BC between 2017 and 2020. Only patients with known HER2 status and available survival data were included. Patients’ sociodemographic and clinicopathological characteristics, and outcomes were collected from medical records. Descriptive statistics were used to analyze sociodemographic and clinicopathological characteristics. X2 tests were used to evaluate associations between HER2 status and other characteristics. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by the log-rank test according to HER2 status. Multivariable adjusted hazard ratios were estimated by Cox regression models. A p value of < 0.05 was considered statistically significant. Results Among 55 patients with metastatic BC, median age at diagnosis was 51 years, 56.4% were postmenopausal and 25.5% had family history of BC. The most frequent histologic subtype was ductal (65.5%), followed by lobular (20%). Approximately 2/3 presented with metastatic disease de novo (67.3%), 69.1% presented with visceral metastases and the median number of lines of treatment was 2. According to intrinsic subtypes 54.5% were luminal HER2-negative (HER2-), 16.4% luminal HER2-positive (HER2+), 10.9% HER2 enriched, and 18.2% triple negative. According to HER2 status, 11 (20%) were HER2+, 26 (47.3%) were HER2-low, and 18 (32.7%) were HER2-. HER2-low expression was more frequent in the hormone-receptor positive (HR+) (51.3%) than in HR negative (HR-) (31.3%), however, this difference was not statistically significant (p = 0.11). Patients’ characteristics according to HER2 status are shown in Table 1. With a median follow-up of 39.9 months, there were no differences in PFS and OS according to HER2 status. Median OS was 45, 30.8, and 46.4 months, for HER2+, HER2-low, and HER2-, respectively (p = 0.48). On univariate analysis, age, menopausal status, RH status, HER2 status, disease presentation and visceral metastases were not associated with improved OS. In patients with HER2-low status, median OS was 36.6 and 15.8 months for patients with HR+ and HR- disease (p = 0.009). In the HER2-low subgroup, multivariate analysis showed that HR status (hazard ratio 10.96 [95% CI 2.11-56.92], p = 0.004) and having received ≥2 lines of treatment (hazard ratio 13.34 [95% CI 1.97-90.37], p = 0.008) were statistically associated with better OS. Conclusion Our findings show that almost half of patients with metastatic BC have a low HER2 expression. Although HER2-low status did not impact survival in a small cohort of Mexican patients, HR status and lines of treatment were associated with better prognosis in patients with HER2-low disease. These results demonstrate the high burden of Mexican patients with HER2-low disease who could benefit from targeted therapies after first line therapy, and the importance of ensuring access to effective treatment options. Table 1. Patient characteristics. Citation Format: Bertha Alejandra Martinez-Cannon, Haydee Cristina Verduzco-Aguirre. Frequency and prognosis of HER2-low status in Mexican patients with metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-58.

Expression of BRCA1 by immunohistochemistry and its association with ER, PR, Her2neu status in infiltrative ductal carcinoma of breast.

Breast cancer is a heterogeneous disease, which differs in its clinical behaviors and responses to treatment and outcome. The prognosis of breast cancer depends on histopathological parameters and molecular subtypes. Among more than 300 genes, which are involved in the pathogenesis of breast cancer tumor suppressor gene such as BRCA1 is known to play a significant role in hereditary cancers. However, its role in sporadic cases of infiltrating ductal carcinoma is yet to be established. To evaluate the expression of BRCA1 in infiltrative ductal carcinoma and to analyze the association of BRCA1 with histopathological parameters and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (Her2) neu expression. This was a laboratory-based exploratory study in which 56 patients with infiltrative ductal carcinoma who underwent radical mastectomy from October 2019 to July 2021 were included. Patients with chemotherapy and radiotherapy, trucut biopsies, and incomplete patient details were excluded. Immunostaining for BRCA1 was performed. Individual clinicopathological parameters were compared with the BRCA1 mutation. Statistical analysis was done using SPSS 22. A P value of < 0.05 was considered statistically significant. Among 56 cases of IDC, 18 cases (32.1%) showed BRCA1 mutation. BRCA1 mutation was associated with postmenopausal age, larger tumor size, lower tumor grade, and higher tumor staging. When we analyzed the biomarkers with BRCA1 mutation, it showed a negative association with ER, PR, and Her2 neu and a high Ki67 proliferation index. No family history of breast carcinoma was seen in 34/56 patients where history was available. Our study showed BRCA1 mutation in 32.1% and associated with postmenopausal age group, larger tumor size, and higher staging and negative hormonal status of breast carcinoma.

Breast Carcinoma in Young Females: A Prospective Study in Terms of Clinicopathological Presentation at a Tertiary Care Center in India.

Introduction: The incidence of breast carcinoma in young women is on the rise, particularly in developing Asian countries like India. Owing to a unique presentation in terms of genetic background, clinical features, and histological characteristics, the prognosis becomes challenging, which therefore entails a detailed study for better understanding and management of the disease. This study aimed to establish the role of clinical and pathological parameters in breast cancer disease in young women.Methods: This was a prospective comparative study conducted at the Department of Surgery, Hamidia Hospital, Bhopal, India, which spanned a total duration of one year between November 2018 and October 2019, and included a total of 98 consecutive in-house breast carcinoma patients. The patients were categorized into two groups based on age, i.e., the young age group (age < 40 years) and the old age group (age ≥ 40 years).Results: Of the patients, 37 fell in the young age group and 61 in the old age group. There was a significant association between positive family history of breast carcinoma and young age (p = 0.01). Estrogen and progesterone receptor positivity was found to be associated more commonly with old age group patients. The proportion of patients with human epidermal growth factor receptor 2 (HER2)/neu over-expression was higher among the young age group. Triple negativity was more frequently observed amongst young age group patients.Conclusion: Hormone receptor analysis should be an absolute part of the initial work-up of breast carcinoma. Raising awareness among women in society should be of paramount importance. Family history is crucial, particularly in young women, and should not be dismissed. With timely presentation and effective diagnosis, a safer state with a relatively better prognosis can be achieved.

Abstract 2214: Disparity in the uptake of risk-reducing surgery after GCRA in Hispanic patients in Latin America and in the United States

Abstract Background: Patients at increased risk of breast (BC) and/or ovarian (OC) cancer can opt for risk-reducing surgeries (RRS). However, there are disparities in access to genomic cancer risk assessment (GCRA) and cancer prevention interventions related to geography, socioeconomic status, and limited public health support. We studied factors that affect the uptake of risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) in Hispanic patients of Latin America (LatAm) and the United States (US). Methods: Hispanic women enrolled in the Clinical Cancer Genomics Community Research Network registry between 1997-2019 who underwent genetic testing, had a personal or family history (FHX) of BC or OC, and had ≥6 months of follow-up data were considered eligible. Demographic and clinical factors associated with risk-appropriate uptake of RRS were considered. Data were analyzed using Fisher’s exact tests and logistic regression models. Results: 1818 patients with a median follow-up of 43 months were studied. Most were from the US (65%), followed by Mexico (21%), Peru (10%), Colombia (2%), and Puerto Rico (2%). Median age at enrollment was 44 years; 81% had a personal history of BC and 5% of OC. Cancer-associated pathogenic variants (PVs) were identified in 459 patients (25%); 409 were in BRCA, 36 had other BC-susceptibility PVs (ATM, CHEK2, PALB2, PTEN, or TP53), and 14 had other OC-susceptibility PVs (BRIP1, MSH2, MSH6, MLH1, or RAD51C). Overall, 449/1715 (26.2%) patients underwent RRM, with a higher rate among patients in the US than those in LatAm (31% vs. 17%, p&amp;lt;0.01); 377/1517 (25%) patients underwent RRSO, with no regional differences observed (24% vs. 27%, p=0.22). The factors associated with undergoing RRM were US residence (OR 2.2; 95% CI 1.7-2.8), age ≤50 (OR 2.2; 95% CI 1.7-2.8), carrying a BC-predisposing PV (OR 3.5; 95% CI 2.8-4.4), positive FHX for BC (OR 1.5; 95% CI 1.2-1.9), and personal history of cancer (OR 3.6; 95% CI 2.4-5.6). In a multivariate model, US residence, age, and previous BC diagnosis remained independent predictors for RRM in BC-susceptibility gene PV carriers, while age was not a significant factor in non-carriers. The factors associated with undergoing RRSO included being a carrier of an OC-predisposing PV (OR 6.3; 95% CI 4.8-8.1), positive FHX for OC (OR 2.1; 95% CI 1.5-2.8), and previous cancer diagnosis (OR 1.7; 95% CI 1.2-2.5). In carriers of OC-susceptibility gene PVs, residing in US and previous cancer diagnosis were independently associated with RRSO, while positive FHX for OC and previous cancer diagnosis were identified as independent factors in non-carriers. Conclusion: There are disparities in the uptake of RRS outside the US. Beyond limitations in resources, understanding the factors associated with undergoing RRS could be key to developing targeted interventions to improve the uptake of risk-appropriate measures in hereditary cancer syndrome patients. Citation Format: Jeffrey N. Weitzel, Yanin Chavarri-Guerra, Ana Ferrigno, Pamela Mora-Alférez, Annette Campbell-Fontaine, Cynthia Villarreal-Garza, Alejandro Mohar-Betancourt, Gubidxa Gutierrez-Seymour, Gary W. Unzeitig, Sandra Brown, Bita Nehoray, Azucena del Toro-Valero, Pamela Ganschow, Ian Komenaka, Yenni Rodriguez, Francisco Gutierrez-Delgado, Kathleen R. Blazer. Disparity in the uptake of risk-reducing surgery after GCRA in Hispanic patients in Latin America and in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2214.

Heritable genomic diversity in breast cancer driver genes and associations with risk in a Chilean population

BackgroundDriver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families.MethodsThe SNPs were genotyped in 486 BC cases and 1258 controls by TaqMan Assay.ResultsOur data do not support an association between rs4685:C > T, rs8853:T > C, or rs1061651:T > C and BC risk. However, the rs12366395-G allele (A/G + G/G) was associated with risk in families with a strong history of BC (OR = 1.2 [95% CI 1.0–1.6] p = 0.02 and OR = 1.5 [95% CI 1.0–2.2] p = 0.02, respectively). Moreover, rs72758040-C was associated with increased risk in cases with a moderate-to-strong family history of BC (OR = 1.3 [95% CI 1.0–1.7] p = 0.02 and OR = 1.3 [95% CI 1.0–1.8] p = 0.03 respectively). Finally, risk was significantly higher in homozygous C/C cases from families with a moderate-to-strong BC history (OR = 1.8 [95% CI 1.0–3.1] p = 0.03 and OR = 1.9 [95% CI 1.1–3.4] p = 0.01, respectively). We also evaluated the combined impact of rs12366395-G and rs72758040-C. Familial BC risk increased in a dose-dependent manner with risk allele count, reflecting an additive effect (p-trend = 0.0002).ConclusionsOur study suggests that germline variants in driver genes TBX3 (rs12366395) and MAP3K1 (rs72758040) may influence BC risk in BRCA1/2-negative Chilean families. Moreover, the presence of rs12366395-G and rs72758040-C could increase BC risk in a Chilean population.

Bilateral Pleomorphic Ductal Carcinoma Of Breast- A Rare Presentation With Its Diagnostic Dilemma

Pleomorphic carcinoma of breast is a rare morphological subtype of Invasive Breast Carcinoma No Special Type (IBC NST), which has histomorphological overlap with other entities. Here we present such a case with bilateral breast involvement in 45 years old nulliparous woman with family history of breast carcinoma. Typical numerous multinucleated cells (&gt;50%) with marked pleomorphism and wide areas of necrosis were histopathological presentation. AE1/AE3 and Vimentin were positive. Ki-67 labelling index was high along with HER2 amplification. Important differentials were IBC NST with Osteoclast-like giant cells, Choriocarcinomatous pattern, metaplastic carcinoma &amp; metastatic disease all of which was ruled out with proper clinical, histological &amp; immunohistochemical approach. Despite the aggressive nature of the neoplasm and presence of adverse prognostic factors, this case responded well with adjuvant chemotherapeutic regimen.International Journal of Human and Health Sciences Vol. 06 No. 02 April’22 Page: 213-216

ULTRASONOGRAPHY AND MAMMOGRAPHIC FEATURES ACTING AS PROXY TO MOLECULAR SUBTYPING OF BREAST CARCINOMA: A CROSS SECTIONAL STUDY

1. AIMS AND OBJECTIVES : Ÿ To determine the correlation between and predict the molecular subtypes of breast carcinoma based on mammography and ultrasound ndings. Ÿ To correlate the different epidemiological features of breast cancer patients with the molecular subtypes of breast carcinoma. 2. Materials And Methods: In our cross-sectional study, 84 biopsy proven cases of breast carcinoma were referred to radiology department. After taking informed consent and in presence of a female attendant, ultrasonography and mammography of the patients were done. All these patients went for surgical excision of the neoplastic mass; and the mass were sent for IHC analysis. Epidemiological data, clinical features, mammographic features and sonographic features were correlated with IHC subtype of the mass and P-Values were found out. P-Value&lt;0.05 was considered to be statistically signicant. 3. Results: Ÿ Among 84 patients, 22 were of Triple Basal Negative subtype, 17 were of Luminal-A subtype, 16 were of Luminal-B (Her-2 negative) subtype, 15 were of Her-2 enriched subtype and 14 out of 84 patients were of Luminal-B (Her-2 positive) subtype. Ÿ IHC correlation between sex distribution, age distribution, age of menarche distribution, achievement of menopause and age of menopause distribution, parity distribution, history of breast feeding, family history of breast carcinoma, history of breast pain, breast ulceration, nipple discharge, quadrant location of breast mass and size of mass showed P-Value &gt;0.05; which was statistically insignicant. Ÿ IHC corelation with mammographic microcalcications, shape of breast mass, margins of breast mass, posterior acoustic pattern of breast masses and vascularity of the breast mass showed P-Value &lt;0.05; which was statistically signicant. 4. Conclusion: Mammographic microcalcication and other features on sonography like shape of the mass, margins of the mass, posterior acoustic features and vascularity of the mass are strongly correlated in predicting the molecular subtype of breast carcinoma.

Abstract P1-15-04: Features of HER2+ metastasic patients (pts) from a prospective registry of advanced breast cancer (ABC), GEICAM/2014-03 (RegistEM)

Abstract Background: The RegistEM study is a non-interventional study that is providing prospective data from around 1900 ABC pts (females and males) diagnosed with advanced disease between 01/Jan/2016 and 31/Dec/2019, either after recurrence or at 1st diagnosis, in 38 Spanish sites representative of the national territory and whose investigators are GEICAM members. Methods: In the current analysis (cut-off date 10/May/2021, ongoing database), we describe the features of 279 pts included in the RegistEM study, with HER2+ (immunohistochemistry [IHQ] 3+, IHQ 2+ and in situ hybridization [ISH]+) tumors at any time of their ABC (5% after the 1st-line therapy). This subgroup has been evaluated because of the interest from a clinical perspective. Multivariate Cox analysis aiming to identify factors associated with overall survival (OS) were built. Results: 279 pts were identified, representing the 15% pts available in the database at the cut-off date. At first ABC diagnosis, 48% pts had recurrent BC (&amp;gt;12 months [mo] from initial BC diagnosis in 93%), 51% de novo metastatic BC and 1% unresectable locally advanced BC (ULABC). The median age was 59 years, 98% were white , 71% postmenopausal and only 1 male was part of this subset. Considering the BC subtype assessed in the most recent tumor lesion before the 1st-line therapy, 264 pts wereHER2 positive (67% with hormone receptor [HR]+). Family history of BC and/or ovarian cancer was reported in 31% pts, and an hereditary-risk genetic test was performed in 25% (66/267 pts). BRCA1/2 and TP53 mutations were reported in 4/20 and 4/19 pts, respectively, and p53 overexpression in 20/46 pts. Lymph nodes (56%), bone (49%), liver (34%), lung (33%), soft tissue (10%) and brain (8%) were the main metastatic sites. Additional data according to HR status and type of ABC are detailed in the table below. In HR- pts, bone metastases were less frequent and lymph nodes metastases more frequent compared to HR+ pts. Visceral disease was present in 68% pts and ≈75% had ≤3 (47% ≤2) locations involved. The most common therapies by line were: 1) 1st-line: CT + dual anti-HER2 blockade (3%), chemotherapy (CT) (almost in all pts taxane-based)+dual anti-HER2 blockade + endocrine therapy (ET) (mainly aromatase inhibitors) (35%), and ET + anti-HER2 blockade or ET + cyclin-dependent kinases 4/6 inhibitors (11%); 2) 2nd-line: anti-HER2 blockade (56%) [mostly an antibody-drug conjugate (90%)], CT + anti-HER2 blockade (18%) and ET + anti-HER2 blockade (14%); 3) 3rd-line: CT + anti-HER2 blockade (55%) and anti-HER2 blockade (22%). The median time-to-progressions to 1st-, 2nd- and 3rd-line were 14, 5, and 4 mo, respectively. A 4th-line therapy was reported in 52% of pts who received a 3rd-line. At database cut-off date, death was reported in 34% of pts. The median OS of this subset of pts was 41 mo (36-49). In a multivariate Cox regression analysis, the following variables were significantly related with worse survival (from ABC diagnosis): Brain (HR=2.62; 95% CI, 1.02-6.73) and Visceral no Brain involvement (HR=2.15; 95% CI, 1.02-4.53) compare to only soft tissue lesions; early stage at first diagnosis (HR=1.77; 95% CI, 1.15-2.73); HR- (HR=1.70; 95% CI, 1.11-2.60) and age (HR=1.04; 95% CI, 1.02-1.07). Conclusions: In this cohort of HER2+ pts with advanced disease, half of them had de novo ABC which was associated with better OS. The median PFS in 1st- and 3rd-line were slightly better in HR+ pts, and in 2nd-line was similar between HR+ and HR- cohorts. HR+181 (67%)HR- 91 (33%)Recurrent EBC134 (48%)ULABC or de novo M1 145 (52%)Time to recurrence &amp;gt;12 mo in EBC pts., n8435125NALocation of metastaticsites, nBoneBrainLiverLungLymph nodesSoft tissue104 10 62 57 90 1829 9 3232 64 1059 15 36 47 51 2278 6 59 46 1056Líne123123123123n180935690492613385521446333Deaths, n211112111161715141584Therapies by line, nET/BT261922101910212100ET12441011022323CT/BT/ET935031038305830CT/BT4017307581552182366924CT3572353711211BT6431373651145143385The most frequent therapies, nCT + dual anti-HER2 blockade + ET8623331551CT + single-agent HER2 blockade + ET522CT + dual anti-HER2 blockade3493644391016252CT + single-agent HER2 blockade4825641588211521CT5573354711411ET*22105212162644ET + HER2 blockade1213411662782Anti-HER2 blockade6431073651145143382Median duration of treatment, mo125585310441064TTP (mo), median (range)15(1-47)5(1-32)5(0-18)11(2-38)5(1-27)4(2-12)12 (1-47)5(1-26)4(0-17)17(2-45)7(1-32)4(1-18)Median PFS, mo14561154------HR: hormone receptor; EBC: early breast cancer; ULABC: unresectable locally advanced breast cancer; M1: metastatic; mo: month; ET: endrocrine therapy; BT: biological therapy; CT: chemotherapy; TTP: time-to-progression; PFS: progression-free survival. *ET includes aromatase inhibitors or selective estrogen receptor degraders, as single-agents or combined with cyclin-dependent kinases 4/6 inhibitors. Citation Format: Isabel Álvarez, Ángel Guerrero-Zotano, Josefina Cruz, Purificación Martínez, María Hernández, César A Rodríguez, Álvaro Rodríguez-Lescure, Silvia Antolín, Encarna Adrover, Raquel Andrés, Catalina Falo, Jose Ignacio Chacón, Ana Miguel, Sonia Servitja, Maria Galán Gramaje, Mireia Margelí Vila, César Gómez Raposo, María Jose Echarri, Rafael Villanueva, Ariadna TIbau Martorell, Silvia Varela Ferreiro, Ruth Campo, Juan Jose Miralles, Susana Bezares, Federico Rojo, Sara López-Tarruella. Features of HER2+ metastasic patients (pts) from a prospective registry of advanced breast cancer (ABC), GEICAM/2014-03 (RegistEM) [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 P1-15-04.

A Clinico-pathological study of Carcinoma Breast and it's management, in a tertiary care hospital in southern India.

Introduction Among the Indian women breast cancer is the most common type, with age adjusted rates goes upto 25.8/100,000 women and mortality is 12.7/100,000 women. MATERIAL AND METHODS A prospective study of 50 patients done at Victoria hospital and Bowring &amp; Lady Curzon Hospital between October2013 to May2015. Once diagnosed by FNAC. Modified radical mastectomy was done in all cases. RESULTS The mean age of presentation was 4th-5thdecade. 28(56%)subjects attained menarche at 12-13years of age, 12(24%) at 10-11years, 10(20%) at 14-15years. 17(34%)patients were 20-24years by the birth of their first child, 13(16%) were 25-29years, 4(7.5%) were 30-34years, 15(30%) were &lt;20years, 1(5%) &gt;35years. All patients had breast-fed. Our study 39(78%) had &lt;4 pregnancies minimum of 1 pregnancy, 11(22%) had &gt;4 pregnancies. 46(92%)patients had no family history of breast carcinoma, 4(8%) had family history. Symptoms were lump in breast in 50(100%)patients, pain in 15(30%), nipple retraction in 6(12%), axillary lump in 5(10%), ulcer in 4(8%) and nipple discharge in 4(8%). Site of occurrence was upper quadrant in 31(62%)cases, central in 7(14%), upper inner in 6(12%), lower inner in 5(10%) and lower outer in 1(2%). 28(56%) had tumour size of 2-5cm and 22(44%) had size &gt;5cm. 33(66%) had regional lymph node involvement and 17(34%). 20(40%) had stage II disease and 30(60%) had stage III. On histopathological examination 42(84%) had invasive ductal carcinoma, 2(4%) medullary carcinoma, 5(10%) colloid carcinoma and 3(6%) infiltrating ductal carcinoma. 64% cases were ER/PR+, 36% were ER/PR-. Post-operatively 3patients had serous discharge and 2patients seroma. Conclusion Breast cancer was predominantly a disease of middle aged, lump in breast is commonest presentation, Invasive ductal carcinoma is common type. We could not establish role of, age at menarche, age at first birth and breast-feeding as risk factors for breast cancer. keywords modified radical mastectomy, FNAC of breast lump, early-advanced breast cancer.