Age Of Breast Cancer Diagnosis Research Articles

Abstract PO4-02-13: Parity and age first full term pregnancy affects the age of breast cancer diagnosis in breast cancer subtypes defined by estrogen receptor and human epidermal growth factor receptor 2

Abstract Background: Reproductive factors like parity and age at first full term pregnancy (FTP1) are found to have an impact on the occurrence of breast cancer (BC) in many epidemiological studies. Importantly, since the 70s, an ongoing trend to postpone FTP1 and have less children is observed. Additionally, there is an increasing trend for breast cancer incidence in young women in the past several decades, which may match the changing exposures to reproductive factors over time. To our knowledge, few studies focus on the association between parity, FTP1 and the age of breast cancer diagnosis. In this study, we aimed at studying the association between age at breast cancer diagnosis and reproductive factors (parity and FTP1) in each of the four breast cancer subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Patients and method: We considered patients who were >34 years old and were diagnosed and/or treated for early BC in University Hospitals Leuven between January 2000 and November 2020. Patient and tumor characteristics were extracted from the patient files. Missing values were filled in by multiple imputation. A linear mixed model with birth cohorts as random effects was built for premenopausal and postmenopausal patients separately to investigate the association between two reproductive factors (parity and age at first full term pregnancy) and age at diagnosis in each of four breast cancer subtypes defined by ER and HER2. ER positivity was defined as >1% of cells staining positive and reflex fluorescence in situ hybridization (FISH) testing was performed for samples that immunohistochemically (IHC) stained for HER2 with IHC score of 2+ or 3+. Parous women are classified into low parity (1 or 2 children) and high parity (≥ 3 children) and FTP1 was divided into < or ≥ 27 years of age. BMI was considered a possible confounder and was corrected for. We first excluded nulliparous people and compared the mean ages at diagnosis in different parity groups and FTP1 groups separately. We created new variable reproductive patterns by taking intersection of parity categories and FTP1 categories. Then the mean ages at diagnosis in parous groups could be compared with the mean age at diagnosis in nulliparous patients. Step down Bonferroni procedure is applied to correct for multiple comparisons. Result: 3039 premenopausal patients and 6569 postmenopausal patients at breast cancer diagnosis were included in the study. Patients with early age at FTP1 have older age at diagnosis in case of ER+HER2+ BC in both premenopausal and postmenopausal group as compared to patients with late FTP1 (Table 1). For premenopausal patients with ER-HER2+, early age at FTP1 was associated with older age at diagnosis in comparison to late age at FTP1. Premenopausal patients with ER+HER2- BC that had low parity and late FTP1 were diagnosed 0.66 years later than nulliparous patients (p= 0,01). Conclusion: In both premenopausal and postmenopausal parous patients with early FTP1, an older age at diagnosis was observed in HER2+ cases only. When compared to nulliparous patients, the combination of low parity and late FTP1 was associated with older age at diagnosis for premenopausal patients with ER+ HER2- BC. Table 1 Differences in mean age at diagnosis between FTP1 groups in parous patients Menopause Subtype Comparison Estimate (difference in mean age at diagnosis) p-value pre ER+HER2+ <27 vs >=27 1,2030 0,0045 ER+HER2- <27 vs >=27 -0,0548 0,7468 ER-HER2+ <27 vs >=27 1,3519 0,0334 ER-HER2- <27 vs >=27 0,4023 0,3326 post ER+HER2+ <27 vs >=27 1,1764 0,0175 ER+HER2- <27 vs >=27 0,0743 0,7069 ER-HER2+ <27 vs >=27 -0,3750 0,6023 ER-HER2- <27 vs >=27 0,3862 0,3815 Citation Format: Jiumeng Zhang, Zhao Liu, Karen Van Baelen, Maja Vangoitsenhoven, Hans Wildiers, Adelheid Soubry, Patrick Neven. Parity and age first full term pregnancy affects the age of breast cancer diagnosis in breast cancer subtypes defined by estrogen receptor and human epidermal growth factor receptor 2 [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 PO4-02-13.

Abstract GS02-04: Surgical Treatment of Women with Breast Cancer and a BRCA1 Mutation: An International Analysis of the Impact of Bilateral Mastectomy on Survival

Abstract Background: Women with breast cancer and a BRCA1 mutation face a high risk of contralateral breast cancer. For this reason, many women with a unilateral breast cancer opt for bilateral mastectomies. Some will have a contralateral prophylactic mastectomy as a second surgery. However, it is not clear to what extent this operation impacts breast cancer mortality. The objective of the current study was to evaluate the differences in survival by surgical treatment in an international cohort of women with a BRCA1 mutation and unilateral breast cancer. Methods: Eligible participants were identified from a large international cohort of women with breast cancer and a BRCA1 mutation, from 26 collaborating centres. Patients with DCIS and stage IV breast cancer were excluded. Patients with synchronous bilateral cancer were excluded. Demographic data were patient reported and clinical and treatment data were collected from medical records. Women were followed from date of breast cancer diagnosis to either date of last follow-up or date of death. Results: There were 2482 eligible participants from 26 centres from 11 countries. The mean age of breast cancer diagnosis was 43.1 years (range 18-70 years). Among those who had a unilateral mastectomy or lumpectomy, the risk of contralateral breast cancer at 20 years was 27.5%. After experiencing a contralateral cancer the hazard ratio for breast cancer death was 2.14 (95%CI 1.43-3.18), P=0.0002. The fifteen-year breast cancer specific survival in the entire cohort was 82.9%. The survival was 78.7% for those who had a unilateral mastectomy, 86.2% for those who had a lumpectomy, and 88.7% for those who had bilateral mastectomies. 529 of the women who initially underwent a unilateral surgery subsequently had a contralateral or bilateral preventive mastectomy in the follow up period. 529 of the women with unilateral surgery had a contralateral or bilateral preventive mastectomy in the follow up period. After adjusting for age of diagnosis, tumor size, nodal status, chemotherapy (yes/no) and preventive mastectomy (time dependent) the hazard ratio for breast cancer mortality for bilateral surgery versus unilateral surgery was 0.78 (95% CI 0.55-1.13), p = 0.19. Discussion: Women with a BRCA1 mutation and breast cancer who develop a contralateral breast cancer have double the risk of mortality compared to women who do not develop contralateral breast cancer. We observed a small non-significant reduction in mortality for those who had bilateral mastectomies as initial treatment, but the cohort will require longer follow up for definitive results. Women with a BRCA1 mutation should be counselled on the risks of contralateral breast cancer and make surgical decisions with this knowledge. Citation Format: Kelly Metcalfe, Jan Lubinski, Jana Soukupová, Rinat Bernstein-Molho, Mina Lee, Evans Gareth, Arvids Irmejs, Robert Fruscio, Cynthia Villareal Garza, Joanne Ngeow, Jennifer Plichta, Rinat Yerushalmi, Steven Narod. Surgical Treatment of Women with Breast Cancer and a BRCA1 Mutation: An International Analysis of the Impact of Bilateral Mastectomy on Survival [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 GS02-04.

Abstract PO2-10-07: Patterns of presentation, treatment and survival for older patients with metastatic breast cancer (MBC): results from a large prospective registry

Abstract Background: The median age of breast cancer diagnosis in the U.S. is 62 years; however, older pts with breast cancer are consistently underrepresented in clinical research. In population-based studies, older pts, particularly those aged 70+, do worse than their younger counterparts at every stage of disease, including stage IV. However, our understanding of patterns of recurrence, treatment patterns, and outcomes for older pts with MBC is limited by a lack of available data. Methods: We identified pts age >60 years seen at least once at a single, NCI-designated cancer center for a diagnosis of MBC between 1999-2022 with 1+ years of follow-up from the time of their metastatic diagnosis. We categorized pts into 5-year age groups (60-65; 66-70; 71-75; 76-80; >80) and two groups of 60-70 and >70. Clinicopathologic characteristics, treatment patterns, reason for treatment discontinuation, and the proportion enrolling on clinical trials were compared by tumor subtype and age group using Chi-Square testing. Median overall survival using Kaplan-Meier method was calculated from the date of initial MBC diagnosis to date of death or last follow-up, examined by tumor subtype and age. Results: The final analytic cohort included 1,115 patients diagnosed with MBC with median follow-up of 2.9 years (1.0-18.5). Median age at MBC diagnosis was 66.3 years (60.0-95.4) and 10% were non-White; disease subtype distribution was the following: 70.7% HR+HER2-, 11.9% HER2+, 17.4% TN. Overall, 22.2 presented with de novo MBC. Presentation of MBC did not vary by ages 60-70 vs. 70+, with no differences in disease characteristics such as grade and disease sites at MBC diagnosis (except for bone). However, the proportion of pts with HR+HER2- disease increased with age, from 69% of MBC in ages 60-70 and 76% in ages >70 (p=.02). In pts with this subtype receiving first-line (1L) therapy (n=783), use of endocrine therapy as 1L (with or without a CDK4/6 inhibitor) increased by age (77.8% in ages 60-65 v. 94.7% in ages >80); use of 1L chemotherapy also varied by age (22.2% in ages 60-65 v. 5.3% in >80). Among pts with HER2+ BC, 89% received a trastuzumab-containing regimen in the 1L setting; in pts with TN MBC, 94% received at least 1L line of chemotherapy. Overall, most pts discontinued 1L therapy for progression, not toxicity, and there was no variation in rates of discontinuation due to toxicity by age with 10.4% noted in both age groups, 60-70 and >70. The proportion of patients receiving 3+ lines of chemotherapy across disease subtype decreased with increasing age (e.g., 54% in ages 60-65 v. 25% in ages >80 among HR+HER2-; 69% in ages 60-65 and 33% in ages >80 among TN MBC). Overall, enrollment on a clinical trial in the MBC setting steadily decreased with older age from 40% in ages 60-65 to 13% in ages >80 (p=.0004). Overall median overall survival differed with increasing age from 4.4 yrs in ages 60-65 to 2.7 yrs in ages >80 (p< 0.005). In descriptive analyses, the proportion of pts alive at 2 yrs was variable. For those ages 60-65, 37.8%, 17.1%, and 42.9% of pts with HR+HER2, TN, and HR-HER2+, respectively were alive at 2 yrs. For those ages >80, 23.7%, 0%, and 0% of pts with HR+HER2-, TN, and, HR-HER2+ disease were alive at 2 yrs. Median survival times were < 2 years for pts with TN regardless of age. Conclusions. In a unique, large prospective cohort of older pts with MBC, we examined detailed information on disease presentation, treatments, and outcomes, lending new information on patterns of care and experiences for older pts with MBC in a modern real-world experience. Limitations include a single center experience and small numbers of older pts with HER2+ and TN disease. Although the oldest pts with MBC had similar disease characteristics as younger pts in our dataset, survival outcomes were poor, particularly for those ages 80+. Therapeutic approaches, likely including improved supportive care, are urgently needed to optimize outcomes in the oldest pts with MBC. Table 1. Outcomes for older pts with MBC Citation Format: Melissa Hughes, Alyssa Patterson, Alexandra Newman, Amanda Higgins, Gregory Kirkner, Janet Files, Molly Skeffington, McKenna Moore, Sarah Strauss, Nicole Kuhnly, Lindsey Crowley, Sara Tolaney, Nancy Lin, Rachel Freedman. Patterns of presentation, treatment and survival for older patients with metastatic breast cancer (MBC): results from a large prospective registry [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 PO2-10-07.

Association of surgery and radiotherapy with risk of thoracic soft tissue sarcoma among older survivors of breast cancer.

e24063 Background: Although breast cancer survivors are living longer, they have an increased risk of treatment-related second cancers including rare but deadly thoracic soft tissue sarcomas (tSTS), such as angiosarcomas, compared with the general population. Limited studies have examined the relationship between surgery type and radiotherapy on tSTS risk, due to the rarity of this event. We undertook this large-scale study to analyze the joint effects of surgery type and radiotherapy with tSTS risk among older breast cancer patients followed in SEER-Medicare. Methods: The SEER-Medicare analytic cohort included 162,507 patients diagnosed with a primary breast cancer between 2000-2017, aged 66-84 years, who survived 1 year, and were followed until 2018. We calculated the cumulative incidence of tSTS and angiosarcoma accounting for competing risks. We then examined the joint effects of breast surgery and radiotherapy receipt (mastectomy + no/unknown radiotherapy, mastectomy + radiotherapy, BCS + no/unknown radiotherapy, and BCS + radiotherapy), with risk of developing any tSTS or angiosarcoma specifically. We also explored the influence of extent of mastectomy (removal of whole breast only, removal of whole breast and chest wall). We calculated hazard ratios (HRs) from multivariable Cox proportional hazard models, with attained age as the time scale, and adjusted for year of diagnosis (2000-2004, 2005-2009, 2010-2017), chemotherapy (yes, no/unknown), and stage (in situ, localized, regional/distant, unknown). Results: Mean age of breast cancer diagnosis was 73.68 (SD: 5.18) years. Patients were diagnosed with in situ (17.74%), localized (59.89%), and regional/distant (21.94%) stage. Median follow-up time was 6.75 years (IQR: 2.00-3.92), and 139 patients developed a tSTS (95 angiosarcomas). By 5 years after diagnosis, cumulative incidence of tSTS was 0.036% (95% CI: 0.027-0.48) and angiosarcomas was 0.019% (95% CI: 0.012-0.029). Compared with patients who received mastectomy + no/unknown radiotherapy, patients receiving mastectomy + radiotherapy were not at elevated risk (HR: 2.18, 95% CI: 0.71-6.70), whereas patients who received BCS without radiotherapy (HR: 3.04, 95% CI: 1.19-7.76) or with radiotherapy (HR: 7.01, 95% CI: 3.55-13.84) were at elevated risk of developing tSTS. Patients who underwent removal of whole breast and chest wall had a lower risk of developing tSTS (HR: 0.32, 95% CI: 0.11-0.94), compared to whole breast only. Nearly all angiosarcomas occurred among patients treated with BCS + radiotherapy. Conclusions: Clinically, these results, while rare, indicate the greatest risk of tSTS observed after BCS + radiotherapy and the need for closer monitoring and heightened awareness of tSTS. Additional studies are needed to investigate biological underpinnings of tSTS and the potential role of other cancer treatments and comorbidities on development of tSTS.

Abstract P6-01-17: A single-center prospective cohort study to evaluate circulating tumor cells as a monitoring tool in women with breast cancer treated with neoadjuvant chemotherapy

Abstract Background The presence of circulating tumor cells (CTCs) among women before and/or after completion of neoadjuvant chemotherapy (NAC) for breast cancer may be associated with an increased risk of recurrence, but limited data is available. Objectives To use the Epic Sciences platform to detect and enumerate CTCs in blood samples from women with a new diagnosis of non-metastatic breast cancer of any subtype both i) prior to commencing NAC, and ii) after completion of NAC and surgery. Methods Inclusion criteria included women of any age with non-metastatic breast cancer of any subtype who have not yet commenced NAC. Those diagnosed with prior invasive cancer at any site (apart from non-melanoma skin cancer diagnosed more than five years prior to enrollment) were excluded. Blood samples were obtained to measure CTCs prior to NAC and after NAC and surgery, respectively. CTC identification was based on immunofluorescence analysis using Epic Sciences platform as previously described (Ueno et al 2017). The presence of CTCs was correlated with clinical/pathological data and treatment response, which were abstracted from patients’ medical records. The association between the presence of CTCs and clinical/pathologic characteristics was tested using Fisher’s exact test for categorical variables and t-test or Wilcoxon rank sum tests for numerical variables. All analyses were performed using the R software package. An ad-hoc preliminary analysis was conducted among the first 34 of 50 participants. Results 41 patients (out of an intended 50) have been recruited to-date. 34 participants have a pre- and/or post-treatment CTC measurement available, but 1 was excluded because it was identified to have metastatic disease shortly after enrollment. Among 33 evaluable patients without metastatic disease, 6 (19%) had triple negative breast cancer (TNBC), 13 (39%) had HER2+ and 13 (39%) had hormone receptor (HR)+/HER2- breast cancer. Most (94%) received anthracycline and taxane-based NAC. The median age of breast cancer diagnosis was 50 (29-75). A total of 53 samples were tested for CTC enumeration (5 mL per sample) including 33 pre-treatment and 20 post-treatment samples. CTCs were detected in 32 samples (n=32/53, 60%), including 24 pre-NAC (n=24/33, 73%) with a median of 0.9 CTCs per mL (0.2-19) and 8 post-NAC and surgery (n= 8/20, 40%) with a median of 0.6 CTCs per mL (0.3-3.3). Among the 24 patients (73%) who had detectable CTCs pre-NAC, 10 had HR+/HER2- (41.7%), 9 had HER2+ (37.5%) and 4 (16.7%) had triple negative disease. Among the 20 patients for whom matched pre- and post-treatment CTC results were available, 16 (80%) had detectable CTCs pre-treatment and 8 (40%) had detectable levels post-NAC and surgery. Among the 8 patients (40%) for whom CTCs were detectable post NAC and surgery, 4 (50%) had HR+/HER2-, 2 had HER2+ (25%) and 2 (25%) had triple negative disease. 3 of these patients had numerically higher CTC levels after completion of NAC and surgery compared to pre-NAC levels, 2 of whom had HR+/HER2- breast cancer and one of whom had TNBC. A total of 7 of 33 patients achieved a pathological complete response (PCR) to NAC, among whom 3 had matched pre- and post-treatment CTC results available; none of these 3 patients had detectable CTCs post-treatment. Conclusions Approximately 3 in 4 women with non-metastatic breast cancer who undergo NAC have detectable CTCs pre-treatment using the Epic Sciences Platform. Of 20 patients with matched pre-/post-treatment results, a high proportion (40%) have persistently detectable CTCs. Hence, CTCs may represent an additional measure of minimal residual disease for patients undergoing NAC for breast cancer. Citation Format: Rania chehade, Arushi Jain, Veronika Moravan, Giuseppe Di Caro, Amanda Anderson, Megan M. Slade, Rick Wenstrup, Ana Elisa Lohmann, William Tran, Katarzyna Jerzak. A single-center prospective cohort study to evaluate circulating tumor cells as a monitoring tool in women with breast cancer treated with neoadjuvant chemotherapy [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 P6-01-17.

Incidence of Breast Cancer and Enterococcus Infection: A Retrospective Analysis.

Enterococci role in the microbiome remains controversial, and researches regarding enterococcal infection (EI) and its sequelae are limited. The gut microbiome has shown to play an important role in immunology and cancer. Recent data have suggested a relationship between the gut microbiome and breast cancer (BC). Patients in a Health Insurance Portability and Accountability Act (HIPAA) compliant national database (2010 - 2020) were used for this retrospective study. International Classification of Disease (ICD) Ninth and Tenth Codes, Current Procedural Terminology (CPT), and National Drug Codes were used to identify BC diagnosis and EI. Patients were matched for age, sex, Charlson comorbidity index (CCI), antibiotic treatment, obesity, and region of residence. Statistical analyses were implemented to assess significance and estimate odds ratio (OR). EI was associated with a decreased incidence of BC (OR = 0.60, 95% confidence interval (CI): 0.57 - 0.63) and the difference was statistically significant (P < 2.2 × 10-16). Treatment for EI was controlled for in both EI and noninfected populations. Patients with a prior EI and treated with antibiotics were compared to patients with no history of EI and received antibiotics. Both populations subsequently developed BC. Results remained statistically significant (P < 2.2 × 10-16) with an OR of 0.57 (95% CI: 0.54 - 0.60). In addition to standard matching protocol, obesity was controlled for in both groups by exclusively containing obese patients, but one group with prior EI and the other without. In obese patients, a lower incidence of BC was shown in the infected group compared to the noninfected group. Results were statistically significant (P < 2.2 × 10-16) with an OR of 0.56 (95% CI: 0.53 - 0.58). Age of BC diagnosis with and without a prior EI was analyzed and demonstrated increased BC incidence with increasing age in both groups, but less in the EI group. Incidence of BC based on region was analyzed, which showed lower BC incidence across all regions in the EI group. This study shows a statistically significant correlation between EI and decreased incidence of BC. Further exploration is needed to identify and understand not only the role of enterococcus in the microbiome, but also the protective mechanism(s) and impact of EI on BC development.

Abstract C039: Influence of patient ancestry on homologous recombination repair deficiency in cancer

Abstract Homologous recombination repair deficiency (HRD) is a common driver of tumorigenesis that carries therapeutic implications, particularly in breast, ovarian, prostate, and pancreatic cancers. The influence of genetic ancestry on the incidence of HRD in these tumors remains to be defined. Previous studies have reported a higher incidence of variants of unknown significance (VUS) in individuals of non-European ancestry. Here, we evaluated the frequency of HR-deficiency within a diverse cohort of 566 patients with breast, prostate, ovarian, or pancreatic cancer. Genetic ancestry was estimated from constitutional whole exome sequencing data using a single nucleotide polymorphism weight model containing five ancestral populations: European, Native American, African, East Asian, and South Asian. Frequencies of clinical genetic testing, germline variants in HR-genes, and tumor HRD were compared between individuals of admixed Native American and European ancestry (n=82) and those of European ancestry (n=378). Admixed Native American/European individuals had a younger age at diagnosis compared to individuals of European ancestry (median 52.4 years (range, 20.8-83.6) vs 62.9 years (range, 20.9-87.9), p&amp;lt;0.0001; two-tailed unpaired t-test), driven by a younger age of diagnosis in admixed Native American/European individuals with breast cancer. 22.6% of patients received genetic testing as part of their clinical care, with an increased rate of genetic testing in admixed Native American/European individuals with breast cancer, consistent with the younger age of diagnosis in this population. Among individuals who received clinical germline testing, there was no significant difference based on patient ancestry in the time from cancer diagnosis until germline testing was performed. In the cohort overall, individuals of admixed Native American/European ancestry and those of European ancestry had a similar frequency of both pathogenic/likely-pathogenic (P/LP) (8.5% vs 6.3%) and VUS (17.1% vs 15.1%) germline variants in HR genes. In breast cancer patients who were younger than 50 years at diagnosis, admixed Native American/European individuals showed a trend toward a higher frequency of P/LP events compared to European individuals (17.6% vs 7.0%, p=0.1722). The frequency of somatic variants in HR genes and the rate of tumor HR-deficiency were similar between patients of admixed Native American/European ancestry and those of European ancestry. In summary, in this retrospective analysis, women of admixed Native American/European ancestry showed a younger age of breast cancer diagnosis and a trend toward increased incidence of pathogenic or likely-pathogenic germline variants in HR genes compared to women of European ancestry. These data support a role for genetic ancestry influencing cancer risk and phenotypes. Additional studies evaluating the impact of genetic ancestry on HRD are needed to reduce disparities in genetic testing and improve application of therapies targeting HRD in diverse cancer populations. Citation Format: Sara A. Byron, Guangfa Zhang, Kimber Slater, Jiaming Zhang, Tyler Izatt, Bryce Turner, Xiao-Yu Xia, Rick A. Kittles, Jonathan J. Keats, Jeffrey M. Trent, Nicholas J. Schork, Lorna Rodriguez-Rodriguez. Influence of patient ancestry on homologous recombination repair deficiency in cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C039.

Abstract C007: Reasons for pursuing genetic testing among young Black women with breast cancer

Abstract Introduction Genetic testing is an increasingly important part of cancer treatment for women with breast cancer diagnosed under age 45. There has been evidence about low testing uptake and barriers to genetic testing for eligible Black women but less is known about motivations for testing. The objective of this study was to assess reasons for pursuing genetic testing among young Black women with breast cancer. Methods Study participants were a population-based sample of self-identified Black women diagnosed with invasive breast cancer at or below age 50, recruited through the Florida and Tennessee state cancer registries. Participants were categorized into tested and not tested groups. Among the tested, participants were asked why they pursued testing and response options included to guide surgical decisions, chemotherapeutic decisions, radiation decisions, or to benefit family. Respondents were categorized into 4 groups: no motivation specified; treatment motivation only; family benefit motivation only; both treatment and family motivation. Logistic regression was used to estimate factors associated with type of motivation. Results In total, 175 women were eligible for inclusion, 135 women had received genetic testing, and 40 had not. Median age of breast cancer diagnosis was 43. Among tested women, 30 (22%) endorsed treatment motivation only, 69 (51%) endorsed family motivation only, and 31 (23%) endorsed both treatment and family motivation. Women who had daughters had higher odds of endorsing being motivated by family benefit (OR 3.87, 95% CI 1.98, 7.57). This relationship was not seen for having sons (OR 0.84, 0.49, 1.83), sisters (OR 0.78, 95% CI 0.34, 1.77) or brothers (0.87, 0.43, 1.73). Among the 40 women who did not receive genetic testing, 24 (60%) indicated a lack of testing recommendation. Conclusions In our investigation, we found that a greater number of Black women were motivated to pursue genetic testing because of the potential benefit to family members rather than to guide treatment decisions. This finding was especially pronounced among women who had daughters. The null relationship between having sons or either gender sibling and motivation driven by family benefit may reflect greater awareness of BRCA associations with female breast cancer and low awareness of male breast and other BRCA associated cancers. Our findings suggest that conversations around the importance of genetic testing may need to go beyond the importance of guiding treatment decisions and include discussions around the potential benefit for family members. Citation Format: Mya L. Roberson, Sonya Reid, Tuya Pal. Reasons for pursuing genetic testing among young Black women with breast cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C007.

Practical Utility of Diagnostic Clinical Breast Examination in the Diagnosis of Breast Cancer.

ObjectivesWe aimed to investigate the effectiveness of physician-performed diagnostic clinical breast examination (DCBE) for the diagnosis of breast cancer in clinical practice and to determine the rates of breast cancer diagnosed with DCBE compared to the results of breast ultrasonography (US), mammography (MG), and histopathology.MethodsIn the retrospective cohort study, the files of female patients diagnosed with breast cancer and admitted to the general surgery outpatient clinics of a university hospital over a 10-year period (2011-2021) were examined. Patients with complete DCBE findings in their files were identified and analyzed (n = 1,091). The examinations of the patients were performed by general surgery specialists with 5-22 years of experience and by radiologists with 4-15 years of experience.ResultsThe mean age of breast cancer diagnosis of the patients was 55.1 ± 13.5 years. While the sensitivity of DCBE was found to be 88.9%, MG sensitivity was 89.8% and breast US sensitivity was 95.1%. Cancer was detected by MG, breast US, and DCBE in 47.9% (n = 523), by breast US and DCBE in 38.9% (n = 424), by MG and breast US in 5.6% (n = 61), by DCBE alone in 3.6% (n = 39), by MG and DCBE in 2.4% (n = 26), and by breast US alone in 1.6% (n = 18). Early-stage breast cancer (p = 0.00) consisted of 73.2% (n = 383) of cancers detected with DCBE, breast US and MG, 74.6% (n = 316) of cancers detected with DCBE and breast US, 93.4% of cancers detected with breast US and MG (n = 57), 92.3% (n = 24) of cancers detected with DCBE and MG, 94.4% (n = 17) of cancers detected with breast US alone, and 69.2% of cancers detected with DCBE alone (n = 27).ConclusionsCBE still maintains its importance in societies where screening participation and awareness of breast cancer are low. A breast cancer diagnosis is often done after a complaint of a palpable mass in the breast, and only then are more advanced-stage breast cancers are seen. CBE is among the important diagnostic methods preventing breast cancer from being overlooked, especially in places where health resources are limited.

The study of genetic and clinicopathological characterisation of Turkish bilateral breast cancer patients

Introduction. Although bilateral breast cancers are a rare condition in the general population, the incidence has increased significantly in BRCA1 and BRCA2 gene carrier breast cancer patients. Besides the genetic susceptibility, many risk factors such as age, first breast cancer diagnosis age, lifestyle, and environmental factors may be effective in the development of this type of cancer. This study aimed to determine BRCA1/2 gene carriage in patients with bilateral breast cancer and to find out the risk factors that may lead to contralateral cancer formation. Material and methods . From 2016 to 2018, in Turkey, we grouped 31 women diagnosed with bilateral breast cancer synchronously and metasynchronously. Analysis of BRCA1 and BRCA2 genes of these women evaluated for clinical and pathological tumour characteristics was performed using the NGS technique. Results. No significant difference was found between the metachronous (MBBC) and synchronous (SBBC) groups in terms of clinical and pathological tumour characteristics. MBBC patients’ age at first diagnosis of breast cancer was lower than SBBC. Also, there was a statistically significant relationship between chronic diseases and MBBC cancers (c2 = 11.519; p = 0.001). In our study, disease-related variants were found only in three patients, and two of these variants were identified the first time in the literature. Conclusion. The risk of bilateral breast cancer of BRCA1/2 carriers increases when the first breast cancer is diagnosed at a young age and there is a significant family history of cancer. MBBC is associated with chronic diseases, and large-scale research will contribute to clarifying this relationship.

Identifying germline APOBEC3B deletion and immune phenotype in Korean patients with operable breast cancer.

Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) is implicated in anti-viral immune response and cancer mutagenesis. Germline APOBEC3B deletion is associated with increased susceptibility to breast cancer. We aimed to evaluate the association between germline APOBEC3B deletion and clinical phenotypes of breast cancer in Korean patients with operable breast cancer. Mononuclear blood cell DNA of 103 patients with operable breast cancer was collected at Seoul National University Bundang Hospital in 2009. The DNA was sequenced to analyze APOBEC3B deletion status. Further, tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor cells were measured using immunohistochemistry. Median age of breast cancer diagnosis was 46 (25-72). In APOBEC3B deletion analysis, 10 (9.7%), 36 (35.0%), and 57 (55.3%) patients were identified as two-copy deletion (A3Bdel/del), one-one copy deletion (A3Bdel/wt), and no deletion (A3Bwt/wt), respectively. For other cancer susceptibility gene alterations, 9 (8.7%) patients were identified as pathogenic variants: RAD51D (n = 1), GJB2 (n = 1), BRCA1 (n = 1), BRCA2 (n = 2), ATM (n = 1), USH2A (n = 1), RET (n = 1), BARD1 (n = 1). We observed no significant association between germline APOBEC3B deletion with any clinicopathologic features of breast cancer, such as age, family history of cancer, and bilateral breast cancer. Further, according to follow-up observations, APOBEC3B deletion was not predictive of disease-free survival. In ER+ subtype, a trend toward better survival was observed in patients with A3Bdel/del genotype as compared to patients with A3Bdel/wt and A3Bwt/wt genotype (log-rank, P = 0.25). In patients with sufficient tumor samples for the assessment of TIL (n = 63) and PD-L1 (n = 71), the A3Bdel/del genotype was significantly associated with high TILs (> 10%) than other tumor genotypes (6/7 patients in A3Bdel/del vs. 13/24 in A3Bdel/wt vs. 15/32 in A3Bwt/wt: Fisher's exact test, P = 0.029). However, PD-L1 expression was not associated with APOBEC3B deletion status (1/7 patients > 1% PD-L1 in A3Bdel/del vs. 4/26 in A3Bdel/wt vs. 8/38 in A3Bwt/wt: P = 0.901). We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3Bdel/del genotype and high TILs suggests that patients carrying this genotype could be potential candidates for immunotherapy.

Does Breast Cancer Increasingly Affect Younger Women?

Breast cancer is the most frequently diagnosed malignant neoplasm among females. The proportion of women diagnosed in the premenopausal period is relatively small. Nevertheless, this is the most commonly diagnosed cancer among young women. The aim of the study was to analyze the incidence rate of breast cancer in a group of young women based on data obtained in the Lower Silesian Voivodeship between 1984 and 2016. A total of 34,251 women with a diagnosis of invasive breast cancer were analyzed. The median age of diagnosis exhibited an upward trend from 57 to 63. The youngest age of breast cancer diagnosis did not decrease. Women up to the age of 24 were sporadically diagnosed. Given the total number of cases, the proportion of women under the age of 39 was approximately 5%, and it did not increase throughout the entire examination period. The major increase in the growth trend during the analyzed period was observed in a group of women aged of 50–69 (regression coefficient: +24.9) and above 70 (regression coefficient +21.2). In a group of women under 40 the regression coefficient was only +4. It seems that breast cancer does not increasingly affect younger women since the risk in this age group remains low. However, an increasing incidence rate of breast cancer is more commonly observed in premenopausal women.

Abstract B24: A rationale for screening for thyroid malignancy in breast cancer patients

Abstract Introduction: An increased incidence of thyroid cancer in breast cancer patients has been demonstrated in the literature. A recent meta-analysis reports odds ratio of developing thyroid cancer after breast cancer to be 1.55 (Nielsen et al., 2016). The USPSTF and ATA recommend against routine thyroid screening for non-high-risk asymptomatic adults. We aim to obtain demographics of breast cancer patients who develop thyroid cancer and assess their malignancies. We use this assessment to discuss the potential impact that routine thyroid screening could have on breast cancer patients. Methods: We performed a literature review using PubMed and Web of Science databases and reviewed abstracts of 352 publications. Papers were excluded for nonrelevance or lack of patient-level data. Relevant papers were fully reviewed and their data were compared to population-level data from the SEER database. We then gathered data on breast cancer patients at our home institution who later developed thyroid cancer. Chart review was performed on medical records with relevant diagnostic codes. Exclusions were made for nonrelevance or lack of information. Patient demographics and breast and thyroid cancer characteristics were obtained. Results: In literature review four papers were used to obtain breast cancer characteristics on 206 patients. Mean age of breast cancer diagnosis (47.07 years) was younger than peak incidence age range for breast cancer reported by SEER registry (75-79 years). There were more patients with ductal carcinoma in situ or infiltrating ductal carcinoma compared to SEER population (97.09% vs. 74.33). Estrogen receptor status was positive less often compared to SEER population (73.23% vs. 80.77). Five papers were used to obtain thyroid cancer characteristics on 230 patients. Mean tumor size was smaller compared to the SEER population (1.017 cm vs. 1.782). There was a higher percentage of nodal involvement (25.90% vs. 19.62) and extrathyroid extension (34.98% vs. 15.37) compared to SEER population. Initial search for home institution breast cancer patients later developing thyroid cancer yielded 108 patients. 39 were included in our study. The majority developed papillary thyroid cancer with a mean tumor size of 0.99 cm. 74.4% were treated with total thyroidectomy. Conclusion: Screening for thyroid malignancy is a contentious topic. Speculation of the impact thyroid cancer screening could have for breast cancer patients has prompted us to identify the characteristics of these patients and their cancers. Literature review suggests that these patients may develop thyroid cancers with increased lymphovascular involvement and increased extrathyroid extension. If true, it may be worth considering a change in thyroid cancer screening guidelines for female breast cancer patients. Current work is focused on developing more definitive conclusions. We are performing a more in-depth chart review and developing a data collaboration via the Southeastern SHRINE research network to gather more data. Citation Format: Brendan C. Stack, Edouard M. Oudin. A rationale for screening for thyroid malignancy in breast cancer patients [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B24.

Abstract PD3-01: Population-based breast cancer risk estimates for predisposition gene mutations: Results from the CARRIERS study

Abstract Germline mutations in several cancer predisposition genes included in hereditary multigene testing panels have been associated with increased breast cancer risk. However, estimates of breast cancer risks for each gene have in large part been derived from studies of high-risk populations enriched for family history of breast and ovarian cancer, young age of breast cancer diagnosis, or founder mutations. The breast cancer risks associated with mutations in many of these genes in the general population remain to be clearly defined. As clinical hereditary cancer genetic testing is already provided to many women at increased risk and may soon be offered to all breast cancer patients, population-based risk estimates associated with predisposition gene mutations will be needed for appropriate clinical management of mutation carriers. The “CAnceR RIsk Estimates Related to Susceptibility” (CARRIERS) consortium of 17 cohort-based case-control, population-based case-control, and family studies focused on estimation of population-based breast cancer risks and penetrance analysis for mutations in known and candidate breast cancer predisposition genes. Germline DNA from 39486 breast cancer cases and 35868 matched controls was subjected to dual bar-coded QIAseq multiplex amplification of 1733 target regions in 37 predisposition genes. Products from sets of 768 samples were pooled and sequenced in each lane of a HiSeq 4000 system. Mutations were called by GATK Haplotype Caller and Verdict. High quality sequence data was obtained for 99.3% of target regions. Here we report on results from 34741 population-based breast cancer cases and 32728 matched unaffected controls. The mean age of breast cancer diagnosis for cases was 61.2 years and mean age for controls was 61.1 years. Overall, 20.9% of cases and 14.3% of controls had a family history of breast cancer. Furthermore, 74.3% of cases and 75.8% of controls were non-Hispanic white, whereas 13.3% of cases and 15.3% of controls were African American. Among cases with tumor information available, 81.7% were ER-positive and 7.7% were triple negative breast cancers (TNBC). We assessed mutation frequencies in 24 genes including 12 established breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, andTP53). The overall mutation frequency was 6.2% in cases and 2.7% in controls. Case-control association analysis after adjusting for study, age, family history of breast cancer, and race/ethnicity showed that BRCA1(OR=7.45; 95%CI:5.24-10.95) and BRCA2(OR=5.31; 95%CI:4.15-6.88) were associated with high risks of breast cancer in the general population. However, PALB2mutations were only associated with moderate risks (OR=3.63; 95%CI:2.57-5.26). ATMmutations conferred attenuated risks (OR=1.83; 95%CI:1.47-2.28) relative to studies of high-risk families or young onset breast cancers. NBNmutations were not associated with increased breast cancer risk. Mutations in BARD1, RAD51C, RAD51Dand XRCC2were specifically significantly associated with moderate risks of ER-negative breast cancer and TNBC, whereas mutations in ATM, CDH1and CHEK2were specifically significantly associated with ER-positive disease. On the basis of these findings age-related absolute breast cancer risks for commonly mutated genes were estimated. Overall, results from the CARRIERS study establish that mutations in predisposition genes are associated with lower risks of breast cancer in the general population than in enriched populations including high-risk families and young onset, bilateral, or multiple primary cases. We anticipate that the results from this study will inform cancer screening and other risk management strategies for women in the general population with mutations in predisposition genes. Citation Format: Fergus J Couch, Chunling Hu, Steven N Hart, Rohan Gnanaolivu, Kun Y Lee, Jie Na, Chi Gao, Nicholas J Boddicker, Bruce Eckloff, Raed Samara, Josh Klebba, Christine B Ambrosone, Hoda Anton-Culver, Paul Auer, Leslie Bernstein, Mia M Gaudet, Christopher Haiman, Esther M John, Susan Neuhausen, Janet E Olson, Tuya Pal, Julie R Palmer, Dale P Sandler, Jack A Taylor, Amy Trentham-Dietz, Celine M Vachon, Clarice Weinberg, Song Yao, Jeffrey N Weitzel, David E Goldgar, Susan M Domchek, Katherine L Nathanson, Peter Kraft, Eric C Polley. Population-based breast cancer risk estimates for predisposition gene mutations: Results from the CARRIERS study [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 PD3-01.

Abstract P4-17-02: Palbociclib in advanced male hormone positive breast cancer

Abstract Background: Male breast cancer (MBC) is rare and accounts for 1% of all breast cancers. Much of the evidence to support the efficacy of CDKi come from clinical trials that have minimal male representation, either because they were excluded or because of very low accrual. Palbociclib in conjunction with aromatase inhibitors (AI) and fulvestrant has recently been approved in men for the treatment of advanced hormone receptor positive (HR+), HER2 negative breast cancer. A recent retrospective review of postmarketing reports and electronic health records showed the efficacy and safety profile of palbociclib in men may be similar to that of women. However, further studies are needed to support this conclusion. We set out to evaluate the response rate to palbociclib in a single institution known to see a high number of male breast cancer patients. Methods: We identified male patients with metastatic breast cancer treated with palbociclib through the MD Anderson Cancer Center Breast Medical Oncology database. The primary objective was to evaluate response rate to palbociclib in male patients with HR +, HER 2 negative breast cancer. Descriptive statistics were used. Response was assessed based on radiographic RECIST criteria version 1.1 Results: We identified 26 men treated with palbociclib from 1/2015 to 4/2018. The median age of breast cancer diagnosis was 54 years (range 25-70). Five patients (19%) presented with de novo metastatic disease. 14 (54%) patients were treated in the first-line, 3 (12%) second-line, and 9 (35%) third-line or greater. Palbociclib was combined with AI+GNRH in 13 pts (50%), fulvestrant+GNRH in 4 pts (15%), letrozole alone in 3 pts (13%), and fulvestrant alone in 6 pts (23%). Response rate was assessed in 25 of the 26 patients. The rate of response was 48% (12 of 25 patients), with 1 patient achieving a complete response (CR), 11 achieving a partial response (PR), 6 with stable disease (SD) and 7 with progressive disease (PD). Response rate was 59% (10/17) for those that received palbociclib in their first or second lines of therapy while response rate was 25% (2/8) if received as third or higher line of therapy. Response rate was higher in those that received palbociclib with letrozole 62.5% (10/16) versus those who received it with fulvestrant 22.2% (2/9). The median duration of response was 3.8 months. The median follow up from initiation of palbociclib was 15 months. The median PFS for all patients was 10.8 months (IQR 4.9-24.5). Those who received 1-2 lines of therapy had a median PFS of 12.4 months (IQR 4.9-24.5), while the median PFS was 9.2 months for those who received 3 or more lines of therapy (IQR 5.0-14.1). Conclusion: Palbociclib provides benefit for MBC patients with the majority of men in this study achieving clinical response to treatment. Citation Format: Oluchi Oke, Jiangong Niu, Akshara Raghavendra, Mariana Chavez-McGregor, Hui Zhao, Debu Tripathy, Sharon Giordano. Palbociclib in advanced male hormone positive breast cancer [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 P4-17-02.

Breast cancer in patients with brca mutation: case series

Introduction: Women who inherit a deleterious mutation in BRCA face substantially increased risks of developing breast cancer, estimated in 70%. Even though the annual screening with magnetic resonance and mammography promotes the early detection of the disease, the gold standard for the primary prevention of breast cancer is still bilateral mastectomy. Objectives: To characterize breast cancer with mutation in the BRCA gene. Method: This is a retrospective study, case series. We included all patients who had tested positive for BRCA mutation and who had a previous or current diagnosis of breast cancer from 1999 to 2019. The study was approved by the Research Ethics Committee of Universidade Federal do Piauí, report n. 2.817.502. Results: We found 10 patients with previous breast cancer, or at the time when they had a mutation in the BRCA gene. They were all female, with mean age of 39.4 years at diagnosis, average of 3.6 cases of cancer in the family. Five (50.0%) were triple negative tumors, mean size of 6.7cm, 9 invasive carcinomas, 2 stage IIIB, 3 cases with invasion and impairment of axillary lymph nodes. Three underwent bilateral salpingo-oophorectomy, and 6 underwent bilateral or contralateral risk-reducing mastectomy procedures. All patients were submitted to chemotherapy, being 6 neadjuvant and 5 associated with radiotherapy. As to type of mutation, 6 presented mutation for BRCA1, and 4 for BRCA2. Two patients died because of the disseminated disease. Only one patient is still being followed-up, after 29 months, with annual mammography, resonance and clinical examination, and did not accept risk-reducing mastectomy or salpingo-oophorectomy. Conclusions: The mean age of breast cancer diagnosis was 39.4 years. Half of the patients were triple negative, and most had mutation in BRCA1. Two patients died because of the disseminated disease.

MTHFR C677T Polymorphism Is Associated with the Risk of Breast Cancer among Kurdish Population from Western Iran

Background: The key enzyme of methylenetetrahydrofolate reductase (MTHFR) is involved in DNA biosynthesis and repair. Objectives: The role of MTHFR C677T polymorphism in susceptibility to breast cancer is controversial. Methods: In the present case-control investigation, 297 individuals consisted of 100 patients with breast cancer and 197 healthy women were studied for MTHFR C677T genotypes, using PCR-RFLP method. Results: The frequency of MTHFR TT genotype was 10% in patients and 3% in controls (P = 0.008). The presence of TT genotype was associated with susceptibility to breast cancer [OR = 1.97, 95%CI: 1.16-3.36, P = 0.012]. The T allele of MTHFR was found in 30% of the patients compared to 27.6% healthy controls (P = 0.024) that enhanced the risk of breast cancer by 1.56 times (95% CI: 1.06 - 2.3, P = 0.024). There were 71 individuals (71%) with the age of breast cancer diagnosis ≤ 51 years old. Comparing patients with the age of cancer diagnosis ≤ 50 years old with those > 51 years old group indicated a higher frequency of MTHFR TT genotype in the latter (20.7%) compared to the first group (5.6%, P = 0.05). Conclusions: Our study demonstrated an association between the MTHFR C677T polymorphism with the risk of breast cancer among population of Western Iran. Also, our study suggests that the MTHFR TT genotype could be a risk factor for breast cancer in postmenopausal women.

Abstract P5-09-05: Hereditary breast cancer beyond BRCA: Clinical and histopathological characteristics in patients with germline CHEK2, ATM, PALB2 and TP53-mutations

Abstract Background The introduction of multi-gene panel testing in the diagnosis of hereditary breast and ovarian cancer (HBOC) has led to an important increase in the detection of breast cancer predisposition genes other than BRCA1 and BRCA2. Methods All individuals who underwent HBOC-testing at our institution since the introduction of multi-gene panel testing were included (March 2016-August 2017). In this retrospective analysis, the BRCA Hereditary Cancer MASTR Plus® panel is used (Multiplicom, Belgium), with sequencing of BARD1, BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, TP53, MRE11A, RAD50, NBN, FAM175A, ATM, PALB2, STK11, MEN1, PTEN, CDH1, MUTYH, CHEK2, BLM, XRCC2, EPCAM, MLH1, MSH6, PMS2, MSH2. In breast cancer patients with a recurrent germline alteration, age and TNM stage at diagnosis, histological subtype, grade of differentiation and molecular surrogate subtype were recorded. Given the low numbers of TP53-carriers diagnosed by HBOC testing, also patients with a germline TP53-mutation diagnosed by targeted sequencing at our institution were included. Statistical analysis were performed with SPSS version 25. Results In 11.9 % of 2806 patients who underwent panel testing, a germline pathogenic alteration was detected. BRCA1 and BRCA2 were the most prevalent alterations, detected in respectively 3.35 and 2.92 % of patients. Germline alterations in CHEK2, ATM , PALB2 and TP53 were detected in respectively 2.5 %, 1.1 %, 0.5 % and 0.1 %. In 1 % of patients, germline alterations were retrieved that only contribute to ovarian cancer risk (BRIP, RAD51C, RAD51D). Germline DNA mismatch repair alterations were detected in 0.39 % of patients. The median age at onset of breast cancer in patients with germline CHEK2-, ATM-, PALB2- and TP53-mutations was 47, 53, 39 and 33 years respectively. The age of breast cancer diagnosis in patients with germline TP53-alterations was significantly younger compared to patients with CHEK2-mutations (p = 0.01), ATM-mutations (p = 0.01) and PALB2-mutations (p = 0.04). In situ carcinomas were diagnosed in respectively 9 %, 11 % and 11 % of patients with CHEK2-, PALB2- and TP53-mutations. Patients with CHEK2, ATM, PALB2 and TP53-alterations were diagnosed with ≥T3-tumors in respectively 13 %, 12 %, 33 % and 22 %. Nodal status at diagnosis was negative in 40-60 % in these 4 subgroups. Upfront metastatic disease was diagnosed only in 2/43 CHEK2-carriers. More than half of the breast cancer diagnoses were luminal tumors in CHEK2-, ATM- and PALB2-carriers, while cases with germline TP53-alterations only presented with luminal cancers in 22 % in our series. Conclusion Almost half of the pathogenic mutations detected in HBOC-genes are alterations in genes other than BRCA1 and BRCA2. CHEK2-mutations are by far the most prevalent, followed by ATM, PALB2 and TP53. The range of the CHEK2- and ATM-population was wider then expected at the lower-age boundary. The age of breast cancer diagnosis in patients with germline TP53-mutations was significantly younger compared to patients with CHEK2-, ATM- and PALB2-mutations. The distribution of the histological subtypes and grade of differentiation was not suggestive of a specific correlation with germline mutation status. Citation Format: Hoste G, D'Hoore P, Legius E, Van Buggenhout G, Floris G, Wildiers H, Han SN, Van Nieuwenhuysen E, Berteloot P, Smeets A, Nevelsteen I, Weltens C, Janssen H, Van Limbergen E, Neven P, Punie K. Hereditary breast cancer beyond BRCA: Clinical and histopathological characteristics in patients with germline CHEK2, ATM, PALB2 and TP53-mutations [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-05.

Abstract P4-03-10: Identifying germline APOBEC3B deletion using hereditary cancer panel in Korean patients with operable breast cancer

Abstract Background: APOBEC3B is a cytosine deaminase implicated in host immune defense to virus and mutagenesis in cancer. Germline APOBEC3B deletion is known as risk factors for breast cancer with hypermutation and immune activation from previous database-based studies. This study was aimed to evaluate the incidence of germline APOBEC3B deletion in Korean patients with operable breast cancer. Method: The copy number variants of germline APOBEC3B deletion was analyzed from leukocyte DNA of 103 breast cancer patients whose bloods were collected in 2009 for pharmacogenomic study at Seoul National University Bundang Hospital. Hybrid-capture based next-generation sequencing panel targeting 53 hereditary cancer genes were used. We also measured tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor or immune cell with a rabbit monoclonal antibody (E1L3N). Results: Median age of breast cancer diagnosis was 46 (25-72). In APOBEC3B deletion analysis, 10 (9.7%), 36 (35.0%), and 57 (55.3%) patients were identified as two-copy deletion (A3Bdel/del), one-one copy deletion (A3Bdel/wt) and no deletion (A3Bwt/wt), respectively. In non-APOBEC3B analysis, 9 (8.7%) patients were identified as pathogenic variant: RAD51D(n=1), GJB2(n=1), BRCA1(n=1), BRCA2 (n=2), ATM(n=1), USH2A(n=1), RET(n=1), BARD1(n=1). We observed no significant association between germline APOBEC3B deletion with any clinicopathologic features of breast cancer such as age, family history of cancer, and bilateral breast cancer. Triple-negative subtype was associated with A3Bwt/wt Tumors (35.1% in A3Bwt/wt vs. 5.6% in A3Bdel/wt vs20% in A3Bdel/del; P=0.018). After a median follow-up time of 92.8 months, APOBEC3B deletion was not predictive of recurrence or survival. In patients with sufficient tumor samples for the assessment of TIL (n=63) and PD-1 (n=71), A3Bdel/del tumor was associated with higher TILs (&amp;gt;10%) than other tumor types (6/7 patients in A3Bdel/del vs. 13/24 in A3Bdel/wt vs. 15/32 in A3Bwt/wt: Fisher's exact test in A3Bdel/del, P=0.029). However, PD-L1 expression was not associated with APOBEC3B deletion status (1/7 patients &amp;gt;1% PD-L1 in A3Bdel/del vs. 4/26 in A3Bdel/wt vs. 8/38 in A3Bwt/wt: P=0.901). Germline APOBEC3B deletion and TILs (n=63) TIL (0-10%)TIL (&amp;gt;10%)TotalA3B(wt/wt)17 (53.1%)15 (46.9%)32A3B(del/wt)11 (45.8%)13 (54.2%)24A3B(del/del)1 (14.3%)6 (85.7%)7 Conclusion: We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3Bdel/del tumor and high TILs suggests that these tumors might be potential candidates for future immunotherapy. Citation Format: Kim SH, Koung Jin S, Kim YJ, Ahn S, Park SY, Chae SM, Kang E, Kim E-K, Kim IA, Kim JH. Identifying germline APOBEC3B deletion using hereditary cancer panel in Korean patients with operable breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-03-10.

Pathological profiles and clinical management challenges of breast cancer emerging in young women in Indonesia: a hospital-based study

BackgroundBreast cancer diagnosed at a young age is often associated with aggressive biology, advanced stage, and unfavorable prognosis. The median age of breast cancer diagnosis in Indonesia is younger (48 vs. 68 years-old in Europe) with a relatively higher proportion of patients younger than 40 years old. Although prognosis and outcome of young breast cancer are well studied in developed nations, research evaluating biological characteristics, delivered treatment, and clinical outcomes is very limited in Indonesia.MethodsWe analyzed all breast cancer patients who underwent surgery at Dr. Sardjito Hospital, Indonesia, in 2012–2017. Details of pathology profiles, treatment administrated, and outcomes, as well as reproductive factors among patients younger than 40 years old, were collected and analyzed. Kaplan-Meier curve was used to assess conditional survival based on baseline characteristics.ResultsFrom the total of 1259 breast cancer patients (median age 51 years), 144 (11.4%) were younger than 40 years old (median age 37 years). Of these young patients, 19 (13.2%) were bilateral and 92 (64%) were diagnosed in advanced stages (stages IIIA-C and IV). Median tumor diameter was 5.5 cm and nodal infiltration was present in 73%. Distant metastasis was found in 16% at the time of diagnosis. Moderate and poor differentiation of tumor were 20.8 and 78.5%, respectively, and lymphovascular invasion was found in 90.3%. Around 40% were hormone receptor-positive, 30.6% human epidermal growth factor receptor 2 positive, and 38.2% triple negative. Patients underwent radical surgery in 121 cases (84%) and breast conserving surgery in 7 cases (4.9%). Adjuvant chemotherapy was administrated in 68% and hormonal therapy in 34%. Progression-free survival was significantly shorter in patients with advanced stage, skin and chest wall involvement (T4), positive lymph node infiltration, positive hormonal receptor, and triple negative subtype (log-rank Mantel-Cox tests, p < 0.05).ConclusionWe found a high frequency of young breast cancer with biologically more aggressive tumors, late diagnosis, frequent relapse, and poor prognosis. Further actions to improve clinical management and meet psychosocial needs in young breast cancer patients are warranted.