Distribution Of Breast Cancer Subtypes Research Articles

Abstract PO4-10-03: Relationship Between Insurance Status and Breast Cancer Care in Young Mexican Women

Abstract BACKGROUND In Mexico, 71% of the population is covered by public health insurance, while 2% are privately insured and 27% are uninsured. Previous studies have demonstrated differences in breast cancer (BC) care according to type of healthcare coverage in the United States and Latin America. Most studies have observed that privately insured patients are diagnosed at earlier stages, have less symptom-to-diagnosis and treatment delays, and have better overall outcomes. The aim of this analysis was to evaluate whether differences in BC care exist among young women with breast cancer (YWBC), ≤40 years at diagnosis, depending on their insurance status in Mexico. METHODS Data was collected from the Mexican prospective cohort of YWBC Joven & Fuerte. Patient surveys and researcher follow-ups were used to collect data related to clinicopathologic features, time from symptom onset to seeking medical assistance and treatment, and perceived quality of information received and medical staff support. Results were analyzed using SPSS. RESULTS Information about health insurance status was available for 608 patients: 565 (93%) had public coverage and 43 (7%) had private coverage. Table 1 describes the clinicopathologic characteristics of both groups. Patients with private insurance were diagnosed at earlier stages, 0-II vs. III-IV (81% vs. 16%), than those with public insurance (50% vs. 45%) (p< 0.001). No difference was found on the distribution of BC subtypes among both groups. A total of 573 (94%) patients had registered information regarding the time from symptom onset to contacting a medical professional. Only 18 (3%) were diagnosed with imaging studies (5% and 3% with private and public coverage, respectively). More privately insured patients (95%) contacted a healthcare professional during the first 3 months since symptom onset than publicly insured patients (74%) (p=0.003). Information regarding the time from contacting a healthcare professional to treatment start was available for 472 (78%) patients. There was no difference in the proportion of patients who started treatment ≤3 months after arriving with a healthcare professional according to type of health insurance (76% private vs. 67% public coverage; p=0.2). The majority of patients (96%) considered having adequate support from the medical staff (100% private vs. 94% public). Compared to those with public coverage, more privately insured patients perceived receiving adequate information about their treatment (79% private vs. 50% public; p< 0.001). There were no differences between groups regarding the perceived quality of information regarding their diagnosis (p=0.06) and continuous BC care (p=0.6). CONCLUSION Patients with private coverage were diagnosed at earlier stages, reported contacting a healthcare professional earlier, and perceived receiving adequate information regarding their treatment more often than patients with public coverage. These results coincide with previously reported differences between patients with private and public health insurance. Interestingly, there were no differences between the delays from the first visit to treatment initiation and perceived support from the medical staff depending on type of healthcare coverage. Given the observed differences between privately and publicly insured patients, population-based interventions to increase awareness of alarm signs for BC and widespread access to quality patient education resources could help decrease the disparities between these groups. Table 1. Clinicopathologic features of BC depending on insurance status Citation Format: David G Gonzalez-Sanchez, Arantxa Ramirez-Cisneros, Alejandra Platas, Alejandra Platas, Daniela Vazquez-Juarez, Fernanda Mesa-Chavez, Ana Ferrigno, Alejandro Mohar, Alan Fonseca, Cynthia Villarreal-Garza. Relationship Between Insurance Status and Breast Cancer Care in Young Mexican Women [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 PO4-10-03.

Abstract PO2-10-04: Clinicopathological Characteristics and Factors Associated With Screening and Late-Stage Diagnosis in Patients With Breast Cancer in Latin America: The LATINA Study (LACOG 0615/MO39485)

Abstract Background: Breast cancer (BC) is the most common malignancy and one of the leading causes of cancer death in women in Latin America (LATAM). However, the region lacks a unified multinational initiative to investigate BC and to further understand regional disparities. Methods: LATINA (LACOG 0615/MO39485) is the first multinational prospective cohort study designed to describe clinicopathological characteristics, treatment patterns, and outcomes of patients with BC in LATAM. Patients aged ≥18 years diagnosed with primary or recurrent BC in the 12 months preceding site activation were included. Data were collected at enrollment and every 6 months for up to 5 years. We present here the results for clinicopathological and demographic characteristics at BC diagnosis. Multivariable logistic regression was performed to investigate characteristics associated with later diagnosis (stage II/III vs. stage I) and detection method (symptomatic vs. screening). Causal mediation analysis was performed to investigate the detection method as a mediator of the effect of health care provision (public or private) on stage at diagnosis. Results: Between February 2020 and August 2022, 3276 patients from 31 research sites in 10 LATAM countries were included. Most patients in this cohort (72.1%, N=2362) were treated in the public health system. Regarding ethnicity, most patients (91.8%, N=3008) self-identified as Latinos and were White (47.3%, N=1549), American Indian (21.0%, N=689), and Black or Brown (16.6%, N=544). The median age at diagnosis was 54 years (range 23–95), 41.8% (N=1368) were < 50 years of age at BC diagnosis, and 54.1% (N=375) of the American Indian patients were ≤50 years of age. BC subtype distribution was: 43.2% (N=1336) luminal A, 14.3% (N=433) luminal B, 22.9% (N=709) human epidermal growth factor receptor 2-positive (HER2+), and 15.4% (N=477) triple negative. In patients older than 50 years old, most cases were detected with symptoms, particularly in the public health system (63.2%, N=836) vs. 50.5% (N=232) in the private health system, p< 0.0001). This was also the case in Black/Brown (61.6%, N=178) and American Indian patients (89.5%, N=281) vs. White patients (45.6%, N=413) (p< 0.0001). In the public system, 37.7% (N=890) and 31.7% (N=748) of cases were diagnosed at stage II and III vs. 37.6% (N=343) and 26.6% (N=243) of cases in the private system, respectively (p< 0.0001). Users of the public health system had a significantly higher risk of being diagnosed with symptoms vs. screening (adjusted odds ratio [aOR] 3.54, 95% CI 2.17–5.76). Causal mediation analysis showed that the detection method (screening vs. symptomatic) mediated 21.8% (95% CI 1.7%–41.9%, p=0.034) of the effect of health care provision (public or private) on stage at diagnosis. Self-identifying as Black (aOR 2.11, 95% CI 1.29–3.45), age < 40 years (aOR 1.97, 95% CI 1.20–3.23), public health care provision (aOR 2.18, 95% CI 1.32–3.59), and a diagnosis of HER2+ (aOR 1.74, 95% CI 1.20–2.52) or triple-negative BC (aOR 2.34, 95% CI 1.47–3.71) were associated with an increased risk of being diagnosed at a later stage. Conclusions: A significant proportion of new BC diagnoses in LATAM is observed in patients < 50 years of age. Reflecting the low screening coverage throughout the region, most patients detect the disease with symptoms. Stage III BC accounted for 30.3% of new cases, being more common among users of the public health system. Differences in the stage at diagnosis related to health care provision (public or private), ethnicity, and country underscore significant disparities that need to be addressed. Further analyses of these data will help identify factors associated with late diagnosis and support the development of regional corrective health policies. Citation Format: Gustavo Werutsky, Cynthia Villarreal-Garza, Henry Gómez, Juan Manuel Donaire, José Bines, Luis Henrique Fein, Maria Clara Horsburgh, Paula Cabrera-Galeana, Heloísa Resende, Rosa Vasallo Veras, Miriam Raimondo, Ricardo Elías Brugés Maya, Vidal Maria Del Rosario, Yeni Nerón, Ana Maria Donoso, Fernanda B. Damian, José D'Oliveira, Couto Filho, Maria Isabel Alonso, Victoria Costanzo, Tomás Reinert, Adriana Elizabeth Borello, Eduardo Cronenberger, Luis Fein, Marcela Urrego, Enrique Alanya, Jorge Luis Soriano García, Saúl Campos-Gomez, Eduardo A. Richardet, Hugo Castro-Salguero, Felipe Cruz, Diego Gómez, Angel Hernández, Carlos Alberto Farfan Tello, Ronald Rodríguez, Rafaela Jesus, Gustavo Gössling, Carlos Barrios. Clinicopathological Characteristics and Factors Associated With Screening and Late-Stage Diagnosis in Patients With Breast Cancer in Latin America: The LATINA Study (LACOG 0615/MO39485) [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 PO2-10-04.

Abstract NG02: Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers

Abstract NG02: Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers

The relationship between 18F-FDG PET/CT parameters and histopathological-immunohistochemical properties in breast cancer

In this study, it is aimed to determine the correlation between histopathologic-immunohistochemical factors, tumor subtypes and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters such standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) in breast cancer (BC). Initial PET/CT examination of 110 histopathologically proven BC patients (age ranging 27-92, mean age 56.18 ± 14.59) were included in this retrospective study. The relationship between histopathological-immunohistochemical factors, tumor subtypes and PET/CT parameters were analyzed by regression analysis. The mean SUV max value of 110 breast tumors was 7.73 ± 5.62 (range 1.4 - 34.15). Histological subtypes were; invasive ductal carcinoma (n:94, 85.5%), invasive lobular carcinoma (n=6, 5.5%) and other types (n=10, 9.1%). The distribution of BC subtypes was as follows; Luminal A (Lum A) (n=38; 34.5%), Luminal B (Lum B) (n=56; 50.9%), HER2-positive (n=3; 2.7%) and Triple Negative (TN) (n=13; 11.8%). Univariate regression analysis revealed significantly higher SUV max values in ductal carcinomas than lobular carcinomas (p=0.03). SUVmax values of the Lum B, HER2 positive and TN groups were higher than Lum A group (p=0.03, p<0.001, p<0.001 respectively). Univariate regression analyses also showed that the MTV and TLG values of TN group were significantly higher than Lum A group (p=0.011, p=0.007, respectively). In multivariate regression analyses, no significant difference was observed in above mentioned groups. MTV, TLG and SUVmax values significantly correlated with histopathological-immunohistochemical factors and tumor subtypes in BC. So that, these parameters can be used to predict the tumors’ behavior.

Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa.

The low overall survival rates of patients with breast cancer in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis, and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients' prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded breast cancer samples, including samples of the "African Breast Cancer-Disparities in Outcomes (ABC-DO) Study," were analyzed. The immune cell phenotypes, their spatial distribution in the TME, and immune escape mechanisms of breast cancer samples from SSA and Germany (n = 117) were investigated using histomorphology, conventional and multiplex IHC, and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TIL) in the 1,237 SSA breast cancer samples, while the distribution of TILs in different breast cancer IHC subtypes showed regional diversity, particularly when compared with German samples. Higher TIL densities were associated with better survival in the SSA cohort (n = 400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in breast cancer samples from Western SSA. Features of nonimmunogenic breast cancer phenotypes were associated with reduced patient survival (n = 131). We therefore conclude that regional diversity in the distribution of breast cancer subtypes, TME composition, and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies. See related Spotlight by Bergin et al., p. 705.

Health-Seeking Behavior Returning to Normalcy Overcoming COVID-19 Threat in Breast Cancer.

The coronavirus disease 2019 (COVID-19) outbreak has significantly impacted the diagnosis and treatment of breast cancer. Our study investigated the change in diagnosis and treatment of breast cancer with the progress of COVID-19 pandemic. The study group comprised 6,514 recently diagnosed breast cancer patients between January 1, 2019, and February 28, 2021. The patients were divided into two groups: pre-COVID-19 period (3,182; January 2019 to December 2019) and COVID-19 pandemic period (3,332; January 2020 to February 2021). Clinicopathological information related to the first treatment after breast cancer diagnosis was retrospectively collected and analyzed in the two groups. Among the 6,514 breast cancer patients, 3,182 were in the pre-COVID-19 period and 3,332 were in the COVID-19 pandemic period. According to our evaluation, the least breast cancer diagnosis (21.8%) was seen in the first quarter of 2020. The diagnosis increased gradually except for the fourth quarter in 2020. While early-stage breast cancer was diagnosed 1,601 (48.1%) during the COVID-19 pandemic (p=0.001), the number of surgical treatments increased 4.6% (p < 0.001), and the treatment time was slightly shorter 2 days (p=0.001). The breast cancer subtype distribution was not statistically different between the pre-COVID-19 and COVID-19 period groups. In the early stages of the pandemic, the number of breast cancer cases temporarily decreased; however, they stabilized soon, and no significant differences could be identified in the diagnosis and treatment when compared to the period before the pandemic.

Abstract P1-05-31: A single center retrospective analysis of 259 cases of metaplastic breast cancer

Abstract Introduction: Metaplastic breast cancer (MBC) is a rare breast tumor.WHO histological classification of breast tumors in 2019 divided MBC into the following seven types: low-grade adenosquamous carcinoma, fibromatoid metaplastic carcinoma, squamous cell carcinoma, spindle cell carcinoma, metaplastic carcinoma with mesenchymal differentiation, mixed metaplastic carcinoma and myoepithelial carcinoma. Based on single center data, this study intends to conduct a detailed analysis of the clinicopathological features, treatment and prognostic factors of MBC. Methods:We collected 259 MBCs treated in our center from 2006 to 2022. The patient’s age, histological type, image feature, tumor size, lymph node metastasis, tumor stage, immunohistochemical information, surgical plan and systemic adjuvant therapy were summarized and considered to explore the factors affecting the overall survival rate (OS) and disease-free survival rate (DFS). T-test and chi-square test were performed on the data. P&amp;lt; 0.05 showed that the difference was statistically significant. Kaplan-Meier survival was used to analyze the long-term efficacy. Results: The incidence rate of MBC in breast cancer patients in our center is about 0.5%. They included 105 cases of squamous cell carcinoma (40.5%), 49 cases of mixed metaplastic carcinoma (18.9%), 41 cases of spindle cell carcinoma (15.8%), 27 cases of metaplasia carcinoma secreting matrix (10.4%), 6 cases of metaplastic carcinoma with mesenchymal differentiation (2.3%), 6 cases of myoepithelial carcinoma (2.3%), 3 cases of low-grade adenosquamous carcinoma (1.2%), 1 case of fibromatoid metaplasia carcinoma (0.4%) and 21 cases of unknown (8.1%). MBC were mainly three negative subtypes, which were 204 cases (78.8%), 41 cases (15.8%) luminal subtypes and 14 cases (5.4%) HER2 positive subtypes. There was no significant difference in the distribution of breast cancer subtypes among different histological types of MBC. There were 63 cases (24.3%) in clinical stage I, 171 cases (66.0%) in stage II, 23 cases (8.9%) in stage III and 2 cases (0.8%) in stage IV. 58 patients underwent core needle biopsy, of which only 7 (12.1%) reported histological types consistent with MBC. Among 154 patients with molybdenum target reports, 59 of them (38.3%) had malignant calcifications. The diagnostic coincidence rates of MRI, ultrasound and molybdenum target were 90.0%, 85.1% and 74.7% respectively. 258 cases of MBC received surgical treatment, including 183 cases of total mastectomy (70.9%), 53 cases of breast conserving surgery (20.5%) and 22 cases of quadrant resection (8.5%); 132 patients (51.2%) underwent axillary lymph node dissection and 93 patients (36.0%) underwent sentinel lymph node biopsy. 24 patients (9.3%) received neoadjuvant chemotherapy, of which only 2 (8.3%) achieved pathological complete remission. 56 patients (21.6%) received adjuvant radiotherapy, with a median of 25 times. 167 patients (64.5%) received adjuvant chemotherapy, and anthracycline sequential paclitaxel was the most commonly used regimen. The median follow-up was 31 months. The five-year DFS was 82.0%, and the five-year OS was 89.4%. Through Cox regression analysis, it was found that patients’ N stage (P=0.036) and receiving anthracycline sequential paclitaxel adjuvant chemotherapy (P=0.004) were independent prognostic factors. Conclusion: The histological types of MBC are complex. MRI is of high value in diagnosis. Conventional CNB is difficult to meet the needs of pathological tissue classification. Patients without lymph node metastasis and receiving anthracycline sequential paclitaxel adjuvant chemotherapy are associated with better prognosis. Through multidisciplinary standardized diagnosis and treatment, there is no significant difference between the prognosis of MBC and the common types of breast cancer. Keyword: metaplastic breast cancer; pathological characteristics; imaging; treatment; prognosis. Citation Format: Douwaner Liu, Jiajian Chen, Shuang Hao, Bingqiu Xiu, Qi Zhang, Liyi Zhang, Guangyu Liu, Zhimin Shao, Jiong Wu. A single center retrospective analysis of 259 cases of metaplastic 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 P1-05-31.

The French Early Breast Cancer Cohort (FRESH): A Resource for Breast Cancer Research and Evaluations of Oncology Practices Based on the French National Healthcare System Database (SNDS).

Simple SummaryBecause of an important disparity of care pathways and quality of care among women diagnosed with an early-stage breast cancer, we aimed to create a unique cohort of patients including all French women aged 18 years or over, treated by surgery and registered in the general health insurance coverage plan. After aggregating and annotating medico-administrative data on 235,368 early breast cancer patients, we open up perspectives for research on adverse effects, morbidity, mortality, the monitoring of care consumption, or medical-economic studies. We describe data sources, inclusion, and exclusion criteria, basic descriptive analyses, and longitudinal trends over time.Background: Breast cancer (BC) is the most frequent cancer and the leading cause of cancer-related death in women. The French National Cancer Institute has created a national cancer cohort to promote cancer research and improve our understanding of cancer using the National Health Data System (SNDS) and amalgamating all cancer sites. So far, no detailed separate data are available for early BC. Objectives: To describe the creation of the French Early Breast Cancer Cohort (FRESH). Methods: All French women aged 18 years or over, with early-stage BC newly diagnosed between 1 January 2011 and 31 December 2017, treated by surgery, and registered in the general health insurance coverage plan were included in the cohort. Patients with suspected locoregional or distant metastases at diagnosis were excluded. BC treatments (surgery, chemotherapy, targeted therapy, radiotherapy, and endocrine therapy), and diagnostic procedures (biopsy, cytology, and imaging) were extracted from hospital discharge reports, outpatient care notes, or pharmacy drug delivery data. The BC subtype was inferred from the treatments received. Results: We included 235,368 patients with early BC in the cohort (median age: 60 years). The BC subtype distribution was as follows: luminal (80.2%), triple-negative (TNBC, 9.5%); HER2+ (10.3%), or unidentifiable (n = 44,388, 18.9% of the cohort). Most patients underwent radiotherapy (n = 200,685, 85.3%) and endocrine therapy (n = 165,655, 70.4%), and 38.3% (n = 90,252) received chemotherapy. Treatments and care pathways are described. Conclusions: The FRESH Cohort is an unprecedented population-based resource facilitating future large-scale real-life studies aiming to improve care pathways and quality of care for BC patients.

143P Demographics of breast cancer and non-malignant breast lesions in Western India: A study of 8000 breast pathologies

Breast cancer accounted for the highest percentage amongst all new cases of cancer in 2020 (11.7%). Different pathologic subtypes have varied survival rates. Benign breast diseases have a reported incidence of 76% in a series in southern India. But in western India, dearth of proper data makes it difficult to predict the distribution. This study intended at creating data on epidemiological distribution of breast cancer subtypes and benign breast lesions in eastern Rajasthan, India.

Factors Associated With the Discussion of Fertility Preservation in a Cohort of 1,357 Young Breast Cancer Patients Receiving Chemotherapy.

PurposeFemale breast cancer (BC) patients exposed to gonadotoxic chemotherapy are at risk of future infertility. There is evidence of disparities in the discussion of fertility preservation for these patients. The aim of the study was to identify factors influencing the discussion of fertility preservation (FP).Material and MethodsWe analyzed consecutive BC patients treated by chemotherapy at Institut Curie from 2011-2017 and aged 18-43 years at BC diagnosis. The discussion of FP was classified in a binary manner (discussion/no discussion), based on mentions present in the patient’s electronic health record (EHR) before the initiation of chemotherapy. The associations between FP discussion and the characteristics of patients/tumors and healthcare practitioners were investigated by logistic regression analysis.ResultsThe median age of the 1357 patients included in the cohort was 38.7 years, and median tumor size was 30.3 mm. The distribution of BC subtypes was as follows: 702 luminal BCs (58%), 241 triple-negative breast cancers (TNBCs) (20%), 193 HER2+/HR+ (16%) and 81 HER2+/HR- (6%). All patients received chemotherapy in a neoadjuvant (n=611, 45%) or adjuvant (n= 744, 55%) setting. A discussion of FP was mentioned for 447 patients (33%). Earlier age at diagnosis (discussion: 34.4 years versus no discussion: 40.5 years), nulliparity (discussion: 62% versus no discussion: 38%), and year of BC diagnosis were the patient characteristics significantly associated with the mention of FP discussion. Surgeons and female physicians were the most likely to mention FP during the consultation before the initiation of chemotherapy (discussion: 22% and 21%, respectively). The likelihood of FP discussion increased significantly over time, from 15% in 2011 to 45% in 2017. After multivariate analysis, FP discussion was significantly associated with younger age, number of children before BC diagnosis, physicians’ gender and physicians’ specialty.ConclusionFP discussion rates are low and are influenced by patient and physician characteristics. There is therefore room for improvement in the promotion and systematization of FP discussion.

Abstract PS18-20: Frequency and spectrum of doublePIK3CAsomatic mutations in metastatic breast cancer patients

Abstract Background: PIK3CA is the most frequently mutated oncogene in breast cancer (BC). These mutations are considered drivers, indeed, several novel PI3K inhibitors are under evaluation in clinical trials. Recently, alpelisib, a PI3Kα inhibitor, combined with hormonotherapy has improved progression-free survival in mutated advanced luminal BC. As a result, alpelisib has been FDA-approved for this setting. In some tumors, double PIK3CA mutations in cis demonstrated increasing oncogenicity and sensitivity to PI3Kα inhibitors compared to those tumors with single-hotspot mutations. We aim at assessing the proportion and distribution of PIK3CA double mutations of a monocentric genomic screening program to select patients for trials with experimental targeted agents. Methods: We assessed PIK3CA mutation in a cohort of 345 consecutive metastatic BC patients diagnosed at Hospital Clínico València-INCLIVA from Jan-13 to Apr-20. Molecular screening of hotspot mutations was performed in primary (36.2%, 125/345) and metastatic tissue (63.8%, 220/345), with either MassArray or Next-Generation Sequencing. Hotspots were selected according to public published databases. To be considered mutant, tumors needed to harbor at least 5% of mutant alleles. Our cohort is enriched in luminal BC, according to clinical trials developing PI3K inhibitors. Results: Patients with PIK3CA mutations represented 34.8% (120/345) of the whole cohort. The distribution of BC subtypes was: 80.5% Luminal, 12.0% HER2, and 7.5% triple-negative. The most frequent metastatic site was liver (32.8%) followed by nodes (21.4%), and bone (11.4%). We detected 27 different hotspots, of which three comprised 73% of all PIK3CA mutations: H1047R (32%), E545K (27%), and E542K (14%). Others hotspots were: E545D (4%), H1047L (3%), M1043I (2%), N345K (2%), C420R (1%), E545A (1%), R88Q (1%). Furthermore, 12% PIK3CA mutations were unique (&amp;lt;1%): R38C, R93Q, R93W, P104R, G106V, E110K, K111E, R115Q, V344G, N345D, N345S, E418K, P539R, E542Q, E453Q, M1043V, and H1047L. In our series, 19 patients (15.8%) of all mutant tumors presented a double PIK3CA mutation. In almost all double-PIK3CA mutated tumors (89%, 17/19), one of the hotspots was either a helical or kinase domain (E542, E545, and H1047). Interestingly, E545D was never detected among tumors with a single-mutations. Conclusions: In our cohort, a wide spectrum of PIK3CA mutations was found in patients with metastatic breast cancer, suggesting the clinical relevance of molecular screening. Double PIK3CA mutations were identified in 15.8% of mutant tumors and maybe related to higher sensitivity to PI3K inhibitors. E545D mutation was always associated with a second mutation suggesting a different biological behavior. Citation Format: Juan Miguel Cejalvo, Santiago Moragón, Valentina Gambardella, Belén Ortega, Cristina Hernando, Maria Teresa Martinez, Noelia Tarazona, Octavio Burgués, Soraya Simón, Jesús Poveda, Alba Viala, Jorge Martín, Pilar Rentero-Garrido, Sheila Zúñiga-Trejos, Ana Lluch, Begoña Bermejo, Desamparados Roda, Andrés Cervantes. Frequency and spectrum of doublePIK3CAsomatic mutations in metastatic breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-20.

Distribution of tumor subtypes in bilateral breast cancer: Comparison between synchronous and metachronous cancer.

This study was performed to evaluate patterns of breast cancer subtypes in Korean patients with synchronous (SBC) or metachronous bilateral breast cancer (MBC). We retrospectively reviewed records of 302 patients with SBC (n=161) or MBC (n=141) who received curative surgery at our hospital between 1995 and 2013. Expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was determined by immunohistochemistry (IHC) staining. We categorized breast cancers into the following subtypes: ER+ or PR+, HER2- (i.e., luminalA); ER+ or PR+, HER2+ (i.e., luminalB HER2+); ER-, PR- and HER2+ (i.e., HER2-enriched); ER-, PR- and HER2- (i.e., triple negative, TN). More patients with MBC were ≤40 years at the time of breast cancer diagnosis than patients with SBC (34.6%vs. 19.3%, P<0.01). The proportion of subtypes in SBC and MBC were as follows: luminalA, 65.8%vs. 45.0%; luminalB, HER2+, 9.0%vs. 8.5%; HER2-enriched, 4.1%vs. 12.1%; and TN, 11.2%vs. 31.2%, respectively (P<0.01). The 10-year overall survival rate in patients with SBC and MBC was 89.0% and 93.6%, respectively. The 10-year disease-free survival rate in patients with SBC and MBC was 79.6% and 80.9%, respectively. Locoregional recurrence was found in 2.5% of patients with SBC and 9.9% of patients with MBC. Distant metastasis occurred in 8.7% of patients with SBC and 4.9% of patients with MBC. The distribution of breast cancer subtypes was different between SBC and MBC. TN-subtype was profoundly more frequent in MBC whereas luminal-subtype was most frequently found among SBC.

188P Impact of HIV infection (HIV+) on baseline characteristics and survival of breast cancer (BC) patients (pts): A systematic review and meta-analysis

The number of HIV+ women diagnosed with BC is increasing. Yet, data are conflicting regarding their stage at diagnosis, distribution of BC subtypes and prognosis. We aimed to assess differences in baseline characteristics and overall survival (OS) between HIV+ vs HIV-uninfected (HIV-) BC pts.

Abstract P6-11-03: Characteristics and survival outcomes of HIV-positive breast cancer patients: A systematic review and meta-analysis

Abstract Background: The number of people living with HIV is increasing worldwide thanks to the use of effective antiretroviral therapy. As these individuals get older, their risk of being diagnosed with cancer increases, including non-AIDS defining cancers such as breast cancer (BC). Most reports reveal that HIV+ patients (pts) with BC tend to be younger than HIV-uninfected (HIV-) pts. However, epidemiological data is yet conflicting regarding tumor stage at diagnosis, distribution of BC subtypes and overall survival (OS) of HIV+ pts as compared to HIV- pts. This meta-analysis aims to assess differences of baseline clinicopathological characteristics and OS of HIV+ vs HIV- BC pts. Methods: We performed a systematic review using MEDLINE, Scielo, and conference abstracts up to June 10, 2019, with no language restrictions. Cohort studies and consecutive series comparing baseline characteristics (age, stage at diagnosis or BC subtypes) and/or OS of HIV+ vs HIV- BC pts were included. BC subtypes were defined according to 2 classifications: 1) “classic” immunohistochemical (IHC) subtypes (ER+/HER2-; HER2+; triple-negative BC); 2) surrogate intrinsic subtypes as per the St. Gallen Consensus (luminal A-like, luminal B-like, HER2-enriched and basal-like). Summary risk estimates (pooled mean ratios [pMR] and odds ratios [pOR]) and 95% confidence intervals (CI) were calculated using random effects models. OS data were pooled as hazard ratios (HR) and 95% CI and modeled using a random effects model. The main endpoints were age (as a continuous variable), stage at diagnosis (early [0-II] vs late [III-IV]), distribution of BC subtypes and OS (using both adjusted and unadjusted HR). Subgroup analysis of each endpoint was performed according to region of the world. Results: A total of 16 studies (4 from North America and 12 from Sub-Saharan Africa [SSA]) published from 2005-2019 were included in this meta-analysis (with 1,764 HIV+ and 1,330,122 HIV- pts). HIV+ pts were younger than HIV- pts (pooled mean age of 41.1 vs 50.5 years, respectively; pMR 0.82, 95% CI 0.76-0.90, p &amp;lt; 0.001) and had a 45% increased risk of presenting with late stage disease (pOR 1.45, 95% CI 1.25-1.68, p &amp;lt; 0.001). There were no differences regarding distribution of BC subtypes, both by the “classic” IHC or by the St. Gallen classification. Overall, HIV+ pts had a 91% increased risk of dying as compared to HIV- pts (adjusted HR for OS: 1.91, 95% CI 1.06-3.45, p = 0.031 and unadjusted HR for OS: HR 1.47, 95% CI 1.10-1.95, p = 0.008). Subgroup analysis of OS according to region of the world showed that, in North America, HIV+ pts had a significantly increased risk of dying as compared to HIV- pts (adjusted HR 2.96, 95% CI 1.06-8.25, p = 0.038). In SSA, the increased mortality risk among HIV+ pts was also significant (adjusted HR 1.59, 95% CI 1.26-2.00, p &amp;lt; 0.001). Sensitivity analysis showed similar findings. Conclusion: This meta-analysis provides for the first time a comprehensive comparison of baseline characteristics and survival outcomes between HIV+ vs HIV- BC pts. Our results consistently demonstrate that HIV+ pts are diagnosed with BC at a younger age and at a more advanced stage. Additionally, even after adjusting for known prognostic factors, HIV+ pts have a worse OS as compared to HIV- pts, not only in developing countries (SSA) but also and particularly in developed countries (North America). There were no apparent differences in terms of distribution of BC subtypes. These results should raise the awareness of clinicians and policy makers regarding the detection and survival gap among HIV+ BC pts. This underserved population should be the focus of more research efforts, in order to better understand the reasons behind these disparities, which can be related to the HIV infection itself, to a more aggressive BC biology, and/or to a lower access to timely diagnosis and effective treatment. Citation Format: Mariana Brandão, Marco Bruzzone, Maria Alice Franzoi, Claudia De Angelis, Daniel Eiger, Rafael Caparica, Martine Piccart-Gebhart, Laurence Buisseret, Marcello Ceppi, Evandro de Azambuja, Matteo Lambertini. Characteristics and survival outcomes of HIV-positive breast cancer patients: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-11-03.

Abstract P5-08-20: Association between quantitative mammographic density and breast cancer subtypes among Chinese breast cancer patients

Abstract High mammographic density (MD) is a strong risk factor for breast cancer; however, data on the association between MD and breast cancer subtypes has been inconsistent and most studies have been conducted using data from Western women. Studies have shown that Asian women, who in general have denser breasts compared with Western women, were more likely to develop luminal B and HER2-enriched tumors. We previously reported that higher MD, assessed using Breast Imaging Reporting and Data System (BI-RADS) categories, was associated with HER2-enriched tumors among Chinese breast cancer patients, which may at least partially explain the higher incidence of HER2-enriched tumors observed in Asian women. Since BI-RADS MD measurement is categorical and known to be subjective, in this study, we aimed to re-evaluate the MD-subtype association using an automated quantitative density metric. The analysis included 1,549 women with invasive breast cancer who were diagnosed and treated in a tertiary hospital in Beijing, China. Subtypes were defined as Luminal A (n=606): ER+ and PR+, HER2-, and low Ki-67 (&amp;lt;30% positive staining)/grade (grades 1 or 2); luminal B/HER2- (n=446): ER+ and/or PR+, HER2-, and high Ki-67 (≥30%)/grade (grade 3); luminal B/HER2+ (n=182): ER+ and/or PR+, HER2+ (regardless of Ki-67/grade); HER2-enriched (n=121): ER-, PR-, and HER2+; Triple-negative (TN, n=194): ER-, PR-, and HER2-. Quantitative measures of MD for the contralateral unaffected breast, including total breast volume, fibroglandular volume, and Volpara Density Grade (VDG, based on predetermined cut-points from volumetric percent density that shows moderate agreement with visual BI-RADS categories), were obtained using VolparaDensity software. Polychotomous logistic regression was used to assess the association between MD (per 1-unit standard deviation increase) and breast cancer subtypes with the adjustment of age, menopausal status, parity, and body mass index (BMI). Compared with luminal A cases, cases with luminal B/HER2- (Odds ratio [OR], 1.15; 95% confidence interval [CI], 1.01-1.32; p=0.04), luminal B/HER2+ (OR, 1.22; 95% CI, 1.02-1.44; p=0.03), and HER2-enriched (OR, 1.32; 95% CI, 1.08-1.60; p=0.01) tumors had significantly higher fibroglandular dense volume, and these associations were stronger in women with normal BMI. In contrast, cases with TN tumors had lower non-dense volume compared with luminal A cases (OR, 0.83; 95% CI, 0.69-1.00; p=0.05). Percent density did not vary significantly by subtypes. When comparing dense versus non-dense breasts using VDG, we found that dense breasts were significantly associated with HER2-enriched tumors (OR, 2.49; 95% CI, 1.40-4.42; p=0.002). Our data suggest that increasing dense volume was associated with luminal B and HER2-enriched subtypes among Chinese breast cancer cases. These results may provide insight into the distinct distribution of breast cancer subtypes in Asian populations. Citation Format: Xiaohong R Yang, Yuan Tian, Jennifer Guida, Hela Koka, Ariane Chan, Changyuan Guo, Erni Li, Eric Tang, Hyuna Sung, Ning Lu, Nan Hu, Gretchen Gierach, Jing Li. Association between quantitative mammographic density and breast cancer subtypes among Chinese breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-20.

Breast cancer subtypes: implications for the treatment and survival of patients in Africa—a prospective cohort study from Mozambique

BackgroundData regarding breast cancer epidemiology, treatment and survival in Africa are scarce. We aimed to assess the distribution of breast cancer subtypes in Mozambique and its impact on patients’ treatment and survival. The concordance of biomarker assessment between cytological and histological samples was also evaluated.MethodsProspective cohort study including 210 patients diagnosed between January 2015 and August 2017, followed to November 2019. Clinicopathological characteristics, treatment, 3-year overall survival (OS) and disease-free survival (DFS) were compared across classic tumour subtypes (oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive and triple-negative breast cancer (TNBC)) and surrogate intrinsic subtypes (St. Gallen classification). Concordance was measured using Cohen’s κ statistics.ResultsA total of 51% of patients had ER-positive/HER2-negative tumours, 24% HER2-positive and 25% TNBC. Concordance between cytological and histological samples regarding ER and HER2 status was substantial (κ=0.762 and κ=0.603, respectively). There were no significant differences across subtypes regarding clinical characteristics and treatment, except for HIV positivity and high histological grade (more prevalent among TNBC) or endocrine therapy (higher use among ER-positive/HER2-negative and HER2-positive patients). Three-year OS was 52.5% (95% CI, 44.3% to 60.0%), being higher in ER-positive/HER2-negative (61.1%) compared with HER2-positive (53.2%) and TNBC (31.9%) patients. Adjusted HRs were 1.96 (95% CI, 1.13 to 3.39) among HER2-positive and 3.10 (95% CI, 1.81 to 5.31) among TNBC versus ER-positive/HER2-negative patients. Three-year DFS was 46.6% (95% CI, 38.0% to 54.8%), being lower among TNBC versus ER-positive/HER2-negative patients (HR 2.91; 95% CI, 1.64 to 5.16). Results were similar between surrogate intrinsic subtypes.ConclusionThere was a high proportion of HER2-positive and TNBC among Mozambican patients and their survival was poor compared with ER-positive/HER2-negative patients, partly due to the limited treatment options. A systematic assessment of ER, PR and HER2 status is feasible and may help tailoring and optimise the treatment of patients with breast cancer in low-resource settings, potentially leading to survival gains in this underserved population.

Distribution of Breast Cancer Subtypes Among Nigerian Women and Correlation to the Risk Factors and Clinicopathological Characteristics.

BackgroundBreast cancer in African women differs from the Caucasian. Understanding the profile of Nigerian women with breast cancer will help with preventive measures and treatment. This study focused on the clinico-pathological characteristics, with risk factors of breast cancer patients in Nigeria.MethodsNewly diagnosed female patients with breast cancer were assessed over 12 months. Patients were reviewed using a predesigned proforma which focused on socio-demographic information, clinical information, risk factors and tumor biology.ResultsA total of 251 women were identified; their mean age was 46 years. More than half (62.5%) are premenopausal at presentation, 37.8% with Eastern Cooperative Oncology Group (ECOG) score of 0 and right side (50.2%) as the most common primary site of disease. Less than half of them (43.0%) are estrogen receptor (ER) positive, 27.9% are progesterone receptor (PR) positive, 43.8% and 47.4% are hormone receptor positive and triple negative, respectively. Most patients presented at the latter stage of the disease, stage III (66.9%) and stage IV (18.3%). Only 15.9% are well differentiated and almost all (92.8%) had invasive ductal histological type. Obesity (66.2%) and physical inactivity (41.9%) are the most common risk factors for the disease. A significant relationship was found between immunohistochemistry status and family history of breast cancer, tumor site, previous breast surgery, previous lump and alcohol intake.ConclusionFindings from this study showed that Nigerian breast cancer patients differ from their counterparts in the high human development index (H-HDI) countries in terms of the patients and disease characteristics. In view of this, prevention and treatment options should consider this uniqueness to ensure better outcome.

Clinical subtypes of breast cancer in Thai women: a population-based study of Chiang Mai province

Abstract Background The change over time of distribution of breast cancer subtypes using population-based data has not been reported. Objective To describe the change over time of the distribution of female breast cancer by clinical subtype among the population in Chiang Mai, Thailand. Methods Data of breast cancer patients from Chiang Mai Cancer Registry, diagnosed from 2004 to 2013 were combined with immunohistochemical status from medical record, and used to describe the proportions of clinical breast cancer subtypes: (1) luminal A-like (ER+/PR+ and HER2-), (2) luminal B-like (ER+/PR+ and HER2+), (3) HER2 (ER- and PR- and HER2+), (4) triple-negative (ER- and PR- and HER2-). The distribution of breast cancer subtypes by age group was also described. Results Among 3,228 female breast cancer cases diagnosed during 2004–2013, the median age was 52 years and most patients presented at the regional stage. The unknown tumor subtype was lower than 25% in the periods 2008– 2009, 2010–2011, and 2012–2013. In those periods, the proportions of luminal A-like were 33%, 36%, and 48%; the proportions of luminal B-like were 14%, 20%, and 16%, the proportions of HER2 were 15%, 14%, and 13%; and the proportions of triple-negative were 16%, 14%, and 13%, respectively. In comparison with other groups, women aged ≥60 years had a significantly higher proportion of luminal A-like (P = 0.001), while women aged &lt;40 years tended to have a higher proportion of triple-negative (P = 0.10). Conclusions The proportion of breast cancer with luminal subtypes is increasing. Thus, in the future, treatment protocols with a variety of hormone therapies should be provided in order to improve efficacy and coverage of treatment for this population.

Abstract B093: 50 gene breast cancer (BC) RNA subtype classifier and colorectal cancer (CRC) CMS subtype classifier applied to 90 prostate cancer (PC) patients reveals distinct subtype differences

Abstract Background: BC and CRC are heterogeneous diseases with several distinct disease subtypes. A 50-gene qPCR assay (PAM50) identifies 5 intrinsic biological subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like in breast cancer. Consensus molecular subtype in CRC (CMS) identifies 4 subtypes: CMS1-4. PC can be classified by specific genomic rearrangements, such as the TMPRSS2-ERG fusion occur or whether specific mutations such as SPOP and FOXA1 or germline BRCA is present, yet 25% of PC remains difficult to classify based on molecular drivers. We used comprehensive genomic and transcriptomic data to determine the association of somatic and germline mutations in molecular PC subtypes using the CMS and 50-gene breast cancer classifiers. Methods: Retrospective analysis on Whole exome (WES) DNA tumor and paired germline and matched deep whole transcriptomic sequencing (RNA-Seq) (∼200x106reads per tumor) data from NantHealth was performed. BC Intrinsic Subtypes and CMS sorting based on RNAseq assay was used to classify PC into 5 BC subtypes and CMS 1-4. Results: 90 PC patients were classifiable using RNAseq and WES DNA. BC subtype distribution was 64.4% Luminal A, 31.1% Luminal B, 2.2% HER2-enriched, 2.2% normal-like, and 0 classified as Basal-like. The CMS subtype distribution was 83.3% CMS4, 15.6% CM1, 1.1% CMS3, and 0 CMS2. Overlap comparison revealed that almost all LumA are CMS4 (56/58, 96.6%) and CMS1 are LumB (11/14, 78.6%). Analysis of germline DDR mutations in LumB compared to LumA showed LumB has significantly more DDR mutants than LumA (OR 2.68, p = 0.035 one-sided Fishers exact test). Conclusions: PC molecularly profiled using 50-gene and CMS classification we found LumA subtype as the predominant subgroup characterized by low TMB and high CMS4. LumB was characterized as higher TMB and greater CMS1 suggesting potential immunotherapy eligibility in this subtype. The presence of potentially pathogenic germline variants in DDR genes is associated with subsequent somatic increase in TMB, however, somatic expression subtyping (by BC or CRC types) is a stronger indicator of TMB than germline pPV in DDR genes. Citation Format: Jacob J Adashek, Sumanta K Pal, Saihitha Veerapaneni, Elias Obeid, Christopher W Szeto, Sandeep K Reddy, Roberto Nussenzveig, Neeraj Agarwal. 50 gene breast cancer (BC) RNA subtype classifier and colorectal cancer (CRC) CMS subtype classifier applied to 90 prostate cancer (PC) patients reveals distinct subtype differences [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B093. doi:10.1158/1535-7163.TARG-19-B093

321P - Clinical application of mutational analysis in breast cancer patients: The relevance of PIK3CA analysis for precision medicine

BackgroundThe identification of biomarkers to drive treatment is one of the most important objectives of precision medicine. During last years, the role of PIK3CA mutations have been related to clinical benefit deriving from treatment with PI3K, and mTOR inhibitors. In breast cancer (BC), PIK3CA mutations are widely present and the use, in clinical trials, of selective inhibitors improved clinical outcomes. The aim of this study is to assess the value of a monocentric genomic screening program to select patients for trials with experimental targeted agents. MethodsWe examined PIK3CA mutation in a cohort of 312 metastatic BC patients diagnosed at Hospital Clínico València-INCLIVA from Jan-13 to Apr-19. The sequencing of hotspot mutations was performed in primary (29.9%) and metastatic tissue (70.1%). We used two different technologies: MassARRAY technology (Sequenom MassARRAY, OncoCarta v1.0) and Iluminia MiSeq System (customised panel, OncoSpot v.1). Hotspots were selected according to databases already published. To be diagnosed as mutated, tumors needed to harbor at least 5% of mutant alleles. 7 clinical trials against PI3K pathway were available. ResultsPIK3CA analysis was performed in 312 paraffin embedded tumor samples, in which only 5.8% the analysis was not possible due to low quality of DNA. The distribution of BC subtypes were 77.6% Luminal, 13.9% HER2, and 8.5% triple negative (TN). PIK3CA mutations were detected in 96 patients (32.7%). In Luminal, PIK3CA mutations reached 36.8% while only 19.5% in HER2 and 16.0% in TN, respectively. A wide spectrum of PIK3CA mutations was found: H1047R (38.5%), E545K (30.2%), E542K (19.8%), R88Q (3.1%), M1043I (3.1%), N345K (2.1%), P539R (1.0%), K111E (1.0%), C420R (1.0%). One hundred and ninety (64.6%) patients were included in clinical trials, and 74 (38.9%) were treated with PI3K, AKT and mTOR inhibitors. ConclusionsPIK3CA mutations were widely present among luminal BC, being actually a specific target for new drugs. PIK3CA mutational analysis was easily and successfully performed in our center. The identification of PIK3CA hotspots mutations lead to the access for our patient to novel drugs into clinical trials, achieving relevant clinical benefits in most of the cases. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureA. Lluch: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Eisai; Advisory / Consultancy: Celgene. A. Cervantes: Advisory / Consultancy: Merk serono; Advisory / Consultancy: Roche; Advisory / Consultancy: Beigine; Advisory / Consultancy: Bayer; Advisory / Consultancy: Servier; Advisory / Consultancy: Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Takeda; Advisory / Consultancy: Astelas; Advisory / Consultancy: Pierre Fabre; Speaker Bureau / Expert testimony: Foundation Medicine. All other authors have declared no conflicts of interest.