History Of Ovarian Cancer Research Articles

Abstract P2-08-28: Breast cancer in young patients undergoing neoadjuvant chemotherapy - A comparison between very young women (less than 30) and young women (31-40 years) - Experience of a cancer center in Brazil

Abstract Introduction Breast tumors (BC) in young patients is frequently diagnosed as a high-grade tumor, at a more advanced stage, hormone receptor negative and Her2 overexpressed. Age is an important risk factor for local recurrence, despite the type of surgery, and is associated to increased risk of metastasis and death. Neoadjuvant Chemotherapy (NeoCT) is the standard of treatment for locally advanced and higher risk tumors (triple negative/TN and HER2 positive). Objectives Observation of BC and prognostic factors in young women submitted to NeoCT in a Brazilian cancer center and to compare age groups (31-40 years of age and below 30 years). Method Retrospective cohort study of women with BC diagnosed at below the age of 40, submitted to NeoCT at a Brazilian cancer center, between 2000-2016. The Residual Cancer Burden (RCB) was used for analysis of the pathological response. P <0.05 was considered statistically significant for Pearson's Chi-square test and Fisher's exact test. Survival analyses were estimated by Kaplan-Meier and the patients were followed for at least 60 months. Results 271 women with BC under the age of 40 were submitted to NeoCT. Of these patients, the age of 217 (80.1%) was between 31-40 years of age, 54 (19.9%) were below 30, and 29.2% had family history of BC or ovarian cancer in first or second degree relatives. Data for clinical staging was 2.2% stage I, 43.1% II, 52.4% III and 2.2% IV (as a single site metastasis). We identified a difference in the stage IV group, with 7.4% (4/54) in the women younger than 30 years and 2.2% (6/217) in the women 31-40 years of age (p 0.035). The most frequent histology was invasive ductal carcinoma, in 87.5% of cases, with histological grades of 2 (35.8%) and 3 (46.9%). Histological subtype revealed 49.1% luminal, 17.7% luminal with 2 superexpressions, 8.1% HER2 and 24.4% TN. We identified a greater proportion of luminal patients in the 31-40 year range (53.9% vs 30.8%) and TN and Her2 in the group younger than 30 years (32.7% and 36.5% vs 22.6% and 23.5%, respectively), p 0.006. Chemotherapy based on anthracyclines and taxanes was used in 76.3% of the cases, with HER2 block when indicated. Dense dose schedules were used in 9.6% of the cases. Complete pathological response (pCR) occurred in 34.7% of the cases, partial response in 45.4%, stable disease in 11.1% and progression during chemotherapy in 1.5% of the cases (2 TN and 2 luminal), not revealing any trend as per age group. Her2 tumors had pCR of 63%, 55% for Her2 luminal, and 53.7% for TN. Conservative surgeries were performed in 78 patients (28.8%) and mastectomies in 193 (71.2%). Sentinel lymph node biopsy was performed in 20.7% of the cases, and lymphadenectomy in 79.3%. 56.9% of patients with conservative surgery and 29.6% of those submitted to mastectomy with pCR. Even with pCR, 94 cases (56.3%) were mastectomized. Of the 251 patients, 37.6% relapsed, 21% distant recurrence, 7% local and 9.1% local and distant, with no variation regarding age group. Of these, 23.1% underwent conservative surgery and 37.4% underwent mastectomy. The response is actually inversely correlated with 15% of patients with pCR, 39.8% of partial responses, 63% of stable diseases and 75% disease progression during treatment. Overall survival was associated to a pathological response, tending to benefit the age range of 31-40 years. Conclusions BC in young patients may have reveal differences as per their age group. In our sample, patients under the age of 30 revealed the most advanced and most aggressive subtypes of BC when compared to women in the 31-40 year group. No distinction was made between NeoCT and relapse, however a survival trend was observed in patients over 30 years of age. No distinction was made between RCB and relapse, but there was a trend of survival in patients over 30 years. Citation Format: Lilian Fraianella, Silvana S Santos, Solange M Sanches, Caroline GA Rocha, Marina De Brot, Fabiana BaroniAlves Makdissi. Breast cancer in young patients undergoing neoadjuvant chemotherapy - A comparison between very young women (less than 30) and young women (31-40 years) - Experience of a cancer center in Brazil [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 P2-08-28.

Abstract P6-08-19: Germline mutation prevalence among US and non-US Hispanic patients undergoing genetic testing for breast and ovarian cancer predisposition

Abstract Background: A variety of studies have examined the prevalence of germline mutations in patients undergoing genetic testing for a wide variety of breast cancer predisposition genes. Many of these studies have focused on patients of Northern European descent, leaving variant prevalence and clinical presentations of patients from underrepresented, and often underserved, populations much less well understood. Our study aimed to examine the prevalence of germline mutations among referred patients from Mexico, Central and South America, as well as a comparative population of Hispanic patients from the United States. Methods: We analyzed a de-identified laboratory-based cohort of patients who had received physician-ordered germline multigene panel test results between December 2014 and June 2019. Inclusion criteria for this study were a personal or family history of breast or ovarian cancer, and either (a) an ordering physician based in Mexico, Central America, or South America, or (b) a Hispanic self-reported ethnicity and a US based ordering physician. For this analysis, Mexican patients were combined with Central Americans. Panel size was per physician discretion, and most (>70%) physicians chose large (at least 20 gene) panels of high- and moderate-risk genes including BRCA1, BRCA2, PALB2, CHEK2, ATM, and TP53, among others. Full gene sequencing and deletion/duplication analysis were performed as described previously [PMID: 26207792] and variants were classified using a framework based on the ACMG/AMP guidelines for variant interpretation [PMID: 28492532]. Results: Of the 25,249 participants who met criteria, 18,513 were self-identified Hispanic-Amercians and 6,736 were non-US participants. Of the non-US group, 6,398 were from South America (including 1200 from Chile and 3781 from Brazil) while 273 were from Mexico and 65 from Central America. Pathogenic or Likely Pathogenic variants were uncovered in 14.4% of all participants, with 1864 findings (representing 7.4% of participants) in BRCA1 or BRCA2, and 1769 (7.0% of participants) in other cancer risk genes. Stratified by location, mutation positive rates were highest among Central (26.9%) and South Americans (19.2%), and lowest among the US Hispanics (12.5%). Based on NCCN guidelines, many of these findings would warrant consideration of a change in care for the patient and/or reflex testing of family members. Conclusions: Cancer patients in Mexico, Central, and South America may have less access to germline genetic testing than patients in (for example) the United States, although our study suggests that Latin American patients and their families can benefit from genetic testing at least at the same rate as Hispanic patients in the US. The higher positive rate among Central and South Americans in this study compared to Hispanic-Americans may be due to referral patterns and cost impact, although this question requires further study. The relative VUS rates between populations, mutation rates for specific clinical presentations, and relevant psychosocial issues also need further study to help maximize the utility of germline genetic testing in Latin America. Citation Format: Stephen E Lincoln, Daniel Pineda-Alvarez, Scott T Michalski, Shan Yang, Edward D Esplin. Germline mutation prevalence among US and non-US Hispanic patients undergoing genetic testing for breast and ovarian cancer predisposition [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 P6-08-19.

A regional population-based hereditary breast cancer screening tool in Italy: First 5-year results.

BackgroundUp to 10% of individuals with breast cancer (BC) belong to families with hereditary syndromes. The aim of this study was to develop an instrument to identify individuals/families at high‐hereditary risk for BC and offer dedicated surveillance programs according to different risks.MethodsThe instrument consisted of a primary questionnaire collecting history of BC and ovarian cancer (OC). This questionnaire was applied to women enrolled in the Emilia‐Romagna Breast Cancer Screening Program. General practitioners (GPs) and specialists could propose the same questionnaire too. Women with a score of ≥ 2, were invited to complete an oncogenetic counseling. According to the Tyrer‐Cuzick evaluation, women considered at high risk were invited to involve the most representative alive individual of the family affected with BC/OC for BRCA1/2 genetic testing.ResultsSince January 2012 and December 2016, 660 040 women were evaluated by the regional screening program, of which 22 289 (3.5%) were invited to the Spoke evaluation, but only 5615 accepted (25.2%). Totally, also considering women sent by GPs and specialists, 11 667 were assessed and 5554 were sent to the Hub evaluation. Finally, 2342 (42.8%) women fulfilled the criteria for genetic testing, and 544 (23.2%) resulted BRCA1/2 mutation carriers.ConclusionsTo our knowledge, this is the first regional population‐based multistep model that is aimed to identify individuals with BRCA1/2 mutations and to offer an intensive surveillance program for hereditary‐high risk women. This tool is feasible and effective, even if more efforts must be performed to increase the acceptance of multiple assessments by the study population.

Healthcare Utilization and Costs after Receiving a Positive BRCA1/2 Result from a Genomic Screening Program.

Population genomic screening has been demonstrated to detect at-risk individuals who would not be clinically identified otherwise. However, there are concerns about the increased utilization of unnecessary services and the associated increase in costs. The objectives of this study are twofold: (1) determine whether there is a difference in healthcare utilization and costs following disclosure of a pathogenic/likely pathogenic (P/LP) BRCA1/2 variant via a genomic screening program, and (2) measure the post-disclosure uptake of National Comprehensive Cancer Network (NCCN) guideline-recommended risk management. We retrospectively reviewed electronic health record (EHR) and billing data from a female population of BRCA1/2 P/LP variant carriers without a personal history of breast or ovarian cancer enrolled in Geisinger’s MyCode genomic screening program with at least a one-year post-disclosure observation period. We identified 59 women for the study cohort out of 50,726 MyCode participants. We found no statistically significant differences in inpatient and outpatient utilization and average total costs between one-year pre- and one-year post-disclosure periods ($18,821 vs. $19,359, p = 0.76). During the first year post-disclosure, 49.2% of women had a genetic counseling visit, 45.8% had a mammography and 32.2% had an MRI. The uptake of mastectomy and oophorectomy was 3.5% and 11.8%, respectively, and 5% of patients received chemoprevention.

Rate of Significant Endometrial Pathology in Women at Low Risk for Endometrial Hyperplasia or Cancer Presenting with Abnormal Uterine Bleeding.

Background and ObjectivesTo determine the rate of significant endometrial abnormalities in premenopausal women at low risk for endometrial hyperplasia and cancer presenting with abnormal uterine bleeding (AUB).Patients and MethodsThis descriptive study was conducted from January 1, 2016 to March 31, 2019. The inclusion criteria were premenopausal women, 35–50 years, presenting with AUB, low risk for endometrial hyperplasia or endometrial cancer, and having undergone endometrial sampling or uterine curettage. Nulliparous, obesity, diabetes mellitus, polycystic ovary syndrome, chronic anovulation, infertility, tamoxifen therapy and/or a family history of uterine, ovarian, breast and colon cancer were excluded. Data regarding baseline characteristics were collected, and histopathology reports were reviewed.ResultsDuring the study period, 644 subjects were recruited, 557 of whom had adequate endometrial tissue for histopathology study. The pathology demonstrated benign in most cases (96%). The rate of significant abnormal endometrial pathology was 4% (23 cases) including 19 cases of endometrial hyperplasia without atypia (3.3%), and 4 cases of endometrial cancer (0.7%).ConclusionThe rate of significant abnormal endometrial pathology in premenopausal women at low risk for endometrial hyperplasia or endometrial cancer presenting with AUB was very low. This information should be incorporated into the counseling process regarding the risks and benefits of endometrial sampling.

9. Factors influencing the success rate of patient derived xenograft formation from breast cancer specimens

Background: Patient derived xenografts (PDX) have been increasingly used as models for cancer research because they more closely resemble the disease than cancer cell lines. However, there is often high cost associated with PDX partly due to its low engraftment rate. Aims: In this study, we aimed to investigate clinicopathological features of specimens from breast cancer patients that may influence success of xenograft formation in mice. Methods: Specimens were obtained from patients at the Royal Prince Alfred Hospital and transplanted into immuno-deficient mice. The mice were monitored for one year to determine whether or not engraftments were successful. Clinicopathological features were correlated with engraftment outcomes. Results: A total of 45 PDX were performed in this study. There were strong negative correlations between engraftment rate and oestrogen receptor and progesterone receptor expression in tumours (p<0.001). Xenograft formation positively correlated with triple negative breast cancer (p<0.001), and high mitotic count of the tumour (p=0.0025). No other significant correlations were found between engraftment rate and other clinicopathological parameters including age, family history of breast or ovarian cancer, grade of tumour, tubule formation, nuclear pleomorphism, lymphatic invasion, HER2 receptor status, Ki-67 proliferative index, or T and N staging. Conclusions: Tumours lacking oestrogen and progesterone receptor expression and with high mitotic counts are more suitable for xenograft formation.

Experts say more women should be tested for BRCA1 and BRCA2 genetic mutations.

New recommendations from the US Preventive Services Task Force (USPSTF) indicate that more women may benefit from genetic testing for the BRCA1 and BRCA2 mutations linked to hereditary breast and ovarian cancer, especially if they have already survived cancer once. The new recommendations, published in JAMA, broaden the scope of who should be evaluated for testing of these mutations.1 They suggest that primary care clinicians assess the risk in women who have a personal or family history of breast, ovarian, fallopian tube, or peritoneal cancer as well as those who have an ancestry associated with BRCA1/BRCA2 mutations. If those patients have a positive result in that risk assessment, they should receive genetic counseling and potentially testing for the mutations, according to the recommendation. Women with no personal or family history of these diseases or ancestry associated with the mutations should not receive routine assessment or genetic counseling and testing, the panel concludes. Fewer than 1% of all women have a mutation in either of the BRCA genes. The recommendation provides guidance regarding the steps women can take to determine whether they are at risk of the mutations, starting with talking to their clinician about their personal or family history and ancestry. The panel adds that women should undergo testing only after they have discussed the benefits and harms with a clinician. The USPSTF is an independent, volunteer panel of national experts in prevention and evidence-based medicine.

Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant.

PurposeRecent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2 mutations using Korean Hereditary Breast Cancer (KOHBRA) study data.Materials and MethodsThe data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study.ResultsThe median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations.ConclusionL1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

Effects of BRCA Germline Mutations on Triple-Negative Breast Cancer Prognosis.

Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I: 47% vs 24.5% in noncarriers), but there was no significant difference in the regional nodal status (58.5–63% with cN0). Contralateral breast cancer developed in 26.5% of BRCA1/2 mutation carriers and in 14% of noncarriers. Other primary cancers were also slightly more common in BRCA1/2 mutation carriers (16.5% vs 9.5%). The performed analysis did not show any significant differences between the groups in recurrence-free survival (p=0.312). There was no significant difference between patients with or without BRCA1/2 mutation as regards overall survival (p=0.649) and the risk of TNBC death (p=0.333). The survival from detection of metastases was similar in two groups (p=0.865). Our study demonstrated that the BRCA1 mutation does not affect TNBC patients' outcomes.

Characteristics predicting recommendation for familial breast cancer referral in a cohort of women from primary care

Family history of breast and related cancers can indicate increased breast cancer (BC) risk. In national familial breast cancer (FBC) guidelines, the risk is stratified to guide referral decisions. We aimed to identify characteristics associated with the recommendation for referral in a large cohort of women undergoing FBC risk assessment in a recent primary care study. Demographic, family history, psychological and behavioural factors were collected with family history questionnaires, psychological questionnaires and manual data extraction from general practice electronic health records. Participants were women aged 30–60 with no previous history of breast or ovarian cancer. Data from 1127 women were analysed with stepwise logistic regression. Two multivariable logistic models were developed to predict recommendations for referral: using the entire cohort (n = 1127) and in a subgroup with uncertain risks (n = 168). Model performance was assessed by the area under the receiver operating curve (AUC). In all 1127 women, a multivariable model incorporating five family history components (BC aged < 40, bilateral BC, prostate cancer, first degree relative with ovarian cancer, paternal family history of BC) and having a mammogram in the last 3 years, performed well (AUC = 0.86). For the 168 uncertain risk women, only paternal family history of BC remained significant (AUC = 0.71). Clinicians should pay particular attention to these five family history components when assessing FBC risk, especially prostate cancer which is not in the current national guidelines.

Utilization of Complementary Alternative Medicine, Diet, and Exercise Among Women at High Risk for Developing Breast Cancer.

Background: Women diagnosed as having a high risk for breast cancer (HR-BC) often seek different health behaviors (HBs) such as complementary and alternative medicine (CAM), diet, and exercise to improve their health and cancer outcome. Methods: Women already enrolled in a multimodality screening study for patients at HR-BC (gene mutation carrier or >20% cumulative lifetime risk) were given a questionnaire to evaluate their use of CAM therapies, diet, and exercise before and after a diagnosis of HR-BC. Patients were also asked to complete the Short-Form 36, State-Trait Anxiety Inventory, and Beck Depression Inventory. Results: A total of 134 (67%) subjects completed the survey from the original cohort. General characteristics included a median age of 46 years (range = 24-73 years), majority were White (91%), BRCA1/2 gene mutation carrier (49%), and prior diagnosis of breast and/or ovarian cancer (30%). Almost all of the patients reported a lifetime prevalence of any HB (97%) and CAM utilization (91%). Subjects also had a high lifetime utilization of exercise (83%), herbs and supplements(72%), and diet programs (58%). All of these HBs declined in utilization after diagnosis of HR-BC by as much as 30%. After diagnosis of a HR-BC, a personal history of breast and/or ovarian cancer was significantly correlated with increased use of CAM (odds ratio [OR] = 5.9, P < .01), herbs and supplements (OR = 4.3, P < .01), and diet program (OR = 4.4, P < .01) in multivariate analysis. Conclusions: HBs such as CAM, diet, and exercise are highly prevalent among women with HR-BC, and the utilization of HB decreases significantly after diagnosis of HR-BC.

Spectrum of germline BRCA mutations in hereditary breast and ovarian cancer syndrome in Indian population: A central reference laboratory experience

Introduction: There is a growing need for BRCA1/BRCA2 mutation frequencies among hereditary breast and ovarian carcinoma (HBOC) cases, specifically determined on the grounds of personal and family history profiles in the Indian population. The current study was intended to identify BRCA1/2 mutation frequency and spectrum in Indian women fulfilling the National Comprehensive Cancer Network criteria.Methods: One hundred and sixty unrelated women were screened for germline variations in BRCA1 and BRCA2 genes by sequencing. The variants were classified as pathogenic or benign on the basis of American College of Medical Genetics (ACMG) guidelines.Results: Of 160 women screened for BRCA mutations, 51 (31.9%) carried a pathogenic variant in BRCA1 (n = 36) or BRCA2 (n = 15) gene. An increased frequency of mutation was seen in women with a personal history of breast or ovarian cancer (34.5%) in comparison to unaffected family members (25%). A spectrum of 34 different pathogenic variants (20 in BRCA1 and 14 in BRCA2) was identified in 51 cases. This included a novel variant c.3683_3684dup in BRCA1 which was categorized as a pathogenic variant. The variant c.68_69delAG in BRCA1 was identified in 12/51 positive cases and appears to be the hotspot mutation in the Indian population. In addition, 11 different missense variants were identified in 10 of the study participants and were categorized as variants of unknown clinical significance (VUS) based on the ACMG guidelines. Of these, three of the variants (c.389A>C in BRCA1 and c.3179G>A and c.10124G>T in BRCA2) were unreported in the published literature.Conclusion: The prevalence of pathogenic variants in the Indian HBOC cohort is high and is similar to other Indian studies. The spectrum of BRCA variants is also diverse, and it is very important to correctly classify them as pathogenic, VUS, or benign. We reinforce the importance of complete BRCA gene screening in the index case, followed by genetic counseling and targeted mutation analysis in other at-risk family members.

Benign breast tumors: epidemiological profile and therapeutic conduct at the escola paulista de medicina

Introduction: Breasts represent an important site for the development of diseases. It is known that 80% of the palpable masses of the breast are of benign origin. Benign breast diseases range from inflammatory to neoplastic processes. Objectives: to evaluate the clinical and epidemiological characteristics of patients diagnosed with benign breast tumor at the Mastology outpatient clinic of the Universidade Federal de São Paulo (UNIFESP). Methods: 1,532 medical records, available on the electronic platform PEP-HUHSP through the ICD D24 (benign breast cancer) and N63 (unspecified breast nodule), of patients referred to the service between July 2008 and July 2017 were reviewed. After applying exclusion criteria, 403 medical records were submitted to data collection and tabulation in Excel, followed by statistical analysis using the IBM SPSS Statistics 23 software. The study in question was approved by the Research Ethics Committee of UNIFESP (CEP UNIFESP), in the Teaching and Research Coordination of Hospital São Paulo – Hospital Universitário/UNIFESP (CoEP of HSP-HU/UNIFESP) and exempted from the application of the Informed Consent by the same organs. Results: In the 9-year period, the following results were obtained: mean age was 39.3 years. Comorbidities: smoking (16.4%), SAH (16.8%) and dyslipidemia (6.3%). Family history of breast and/or ovarian cancer accounted for 16.6%. Mean age of menarche and menopause, respectively, were 12.7 and 42.5 years. Causes of referral: "alteration in image examination" (38.3%), "lump in the breast" (33.3%), "follow-up due to previous nodules" (16.5%). Anatomopathological report: fibroadenoma (41%), breast cysts (16%), phylloid tumors (3%), and papilloma (1%). Mean number of consultations per patient until discharge or abandonment of follow-up: three. Choice behavior: expectant (85.2%). Conclusion: The epidemiological profile of patients referred to the UNIFESP tertiary mastology service was mainly composed of women of childbearing age and nulliparous women, whose main comorbidities were smoking and SAH, in the great majority with no family history of breast cancer. Regarding the consultation, the main reason for referral is the findings on imaging exams, and, specially, patients would bring their breast USG along, which surpassed mammography by 34.1%. The choice for biopsy was restricted, present in approximately 1/3 of the cases, but pointed out that the most prevalent nodule is fibroadenoma, followed by phylloid and papilloma tumors. Nevertheless, there was a predilection for expectant conduct. On average, there were regular follow-ups for 1.5 years, followed by a significant dropout rate.

Risk-reducing adenomastectomy: series of 124 procedures carried out in brazilian patients

Objective: Women with mutations in breast cancer predisposition genes have a significantly higher lifetime risk of developing breast cancer and can opt for risk-reducing mastectomy. Women with positive family history of cancer can also opt for prophylactic surgery as a preventive method in selected cases. Current studies showed reduced risk of developing breast cancer after prophylactic nipple-sparing mastectomy; however, despite the good clinical outcomes, one of the main concerns regarding nipple-sparing mastectomy (NSM) is the oncologic safety and nipple-areola complex preservation. In this study, we aimed to evaluate the indications, complication rates and unfavorable events of 62 Brazilian patients who underwent 124 risk-reducing NSM from 2004 to 2018. Methods: Patient data was reviewed retrospectively and descriptive statistics were utilized to summarize the findings. Results: The mean patients’ age was 43.8 years. The main indication for risk-reducing NSM was the presence of pathogenic mutation (53.3%), followed by atypia or lobular carcinoma in situ (25.8), and family history of breast cancer and/or ovarian cancer (20.9%). There were four (3.2%) incidental diagnosis of ductal carcinoma in situ and one invasive ductal carcinoma (0.8%). From the 124 prophylactic NSM performed, two (1.6%) complications occurred: one (0.8%) infection and one (0.8%) partial nipple necrosis. In a mean follow-up of 50 months, there was one (1.6%) newly diagnosed breast cancer in the 62 patients undergoing prophylactic NSM. Conclusions Our findings demonstrated efficacy and safety to perform NSM as prophylactic surgery with good oncologic outcomes and low complication rates in a case series of Brazilian patients.

Germline mutations in Thai patients with nonmucinous epithelial ovarian cancer.

BACKGROUNDGenetic testing is widely recommended for all epithelial ovarian cancer (EOC) patients. However, an increased probability of identifying germline mutations has been reported in selected patients with risk factors such as a family history or personal history of cancer and high-grade serous carcinoma (HGSC) subtype. HGSC has been reported to be the most common subtype of EOC worldwide (approximately 70%). However, this subtype is less prevalent in Thai patients (reported as only 20%). The difference in the distribution of various subtypes of EOC may reflect the incidence of germline mutations in Thai EOC patients.AIMTo evaluate the frequencies of germline mutations in EOC patients and to compare the frequencies in those with and without clinical risk factors for hereditary ovarian cancer.METHODSThis cross-sectional study included 112 nonmucinous EOC patients who underwent primary surgery at our tertiary care hospital. Clinical risk factors for hereditary ovarian cancer were defined as follows: Age below 40 years, a significant family history of cancer, synchronous ovarian and endometrial cancer, and HGSC. Comprehensive germline mutations were detected by next-generation sequencing.RESULTSOf a total of 112 patients, 82 (73.2%) patients had ≥ 1 risk factor and 30 (26.8%) patients had no risk factors. Germline mutations were detected in 26 patients: 20 (17.8%) patients had BRCA1/2 mutations, but 6 (5.4%) patients had mutations in other genes, including 1 in MLH1, 1 in MSH2, 1 in RAD51C, 2 in ATM and 1 in CDH1. Germline mutations were only detected in patients with risk factors (26 of 82, 31.7%), not in patients without risk factors (P < 0.001). A significant family history of cancer and HGSC were the only two significant risk factors associated with a higher proportion of germline mutations (56.3% vs 10% for those with and without a history of cancer, respectively, 40.8% vs 9.5% for those with and without HGSC). Germline BRCA mutations were detected in 38.8% of patients with HGSC but in only 1.6% of those with non-HGSC. An age below 40 years, personal history of breast cancer, and synchronous ovarian and endometrial cancer were not significant factors (14.3% vs 23.5%, 33.3% vs 21%, 22.2% vs 22.3%).CONCLUSIONApproximately one-third of EOC patients with risk factors had germline mutations. Almost all germline BRCA mutations were found in patients with the HGSC subtype. Selected patients with HGSC and a family history of cancer should be initially considered for genetic analysis in Thailand.

Abstract AP04: INCREASING ACCESS TO GENETIC TESTING FOR HEREDITARY BREAST AND OVARIAN CANCER: EXPERIENCE FROM HIGH-VOLUME OB/GYN CLINIC IN TEXAS

Abstract INTRODUCTION: Currently most genetic testing for hereditary cancer risk is performed on individuals with strong personal and/or family histories of cancer. However, as much as 50% of people with a BRCA1 or BRCA2 gene mutation may not have significant family history. As a result, many people are often not identified as having a pathogenic mutation until after they or someone in their family has already been diagnosed with cancer. This study aims to provide insights into prevention of hereditary breast and ovarian cancer by providing broad access to testing in the ob/gyn care setting. METHODS: We describe the demographics and genetic results of 1,113 individuals who were referred by a physician to receive genetic testing for hereditary cancer risk from Color Genomics. The test is a next generation sequencing (NGS) based assessment of 30 genes associated with hereditary cancer risk. The physicians offered the Color Test to their patients at their wellness visit and provided education about genetic testing via online newsletter to inform patients and increase interest for the program. The OB/GYN practice consists of 22 clinicians and serves almost 50 thousand patients. RESULTS: More than 48,253 patients were sent information about this genetic testing via email. The email open rate was 39.6%. 1,113 individuals underwent testing. In the cohort, a total of 90 pathogenic or likely pathogenic variants were identified for an overall pathogenic rate of 8.1%. Twenty individuals (1.8%) were identified as having mutations in genes that increased risk of ovarian cancer (BRCA1, BRCA2, BRIP1, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51C, RAD51D, STK11 and TP53). The average age of the participant who underwent testing was 44.4 years of age. The cohort was 44% Caucasian. Nineteen patients reported Ashkenazi Jewish (AJ) ancestry; the pathogenic rate among people who indicated AJ ancestry was 21%. Health history was self-reported and 47 individuals reported a history of cancer. Only two individuals reported a personal history of ovarian cancer--both were negative for any pathogenic mutations. CONCLUSIONS: The cohort analyzed here included a broader population than has historically qualified for or been offered genetic testing for hereditary cancer risk. The approach taken by this OB/GYN practice highlights a novel way to identify people at increased risk for cancer due to inherited mutation. The practice identified 90 patients who were at increased risk for cancer, including 20 women who were at increased risk for ovarian cancer—none of whom were yet affected—highlighting the opportunity for prevention of ovarian cancer as well as other cancers. Citation Format: Carmelina Heydrich, Lily K Servais, Sarah A Popelka, Brian K Moreau, Katie N Allio, Anjali D Zimmer. INCREASING ACCESS TO GENETIC TESTING FOR HEREDITARY BREAST AND OVARIAN CANCER: EXPERIENCE FROM HIGH-VOLUME OB/GYN CLINIC IN TEXAS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP04.

Abstract DP-013: DEVELOPMENT AND VALIDATION OF CIRCULATING CA125 PREDICTION MODEL IN POSTMENOPAUSAL WOMEN WITHOUT OVARIAN CANCER

Abstract BACKGROUND: Cancer antigen 125 (CA125) is a membrane bound glycosylated mucin which has been reported to be the most promising biomarker for ovarian cancer screening. However, results from two large randomized trials comparing screening with CA125 and transvaginal ultrasound to usual care have shown no clinically significant difference in ovarian cancer mortality. A major limitation of CA125 as an ovarian cancer screening biomarker has been low specificity and variation between individuals by personal characteristics. Identifying personal characteristics that influence CA125 levels could be used to create personalized thresholds for CA125 thereby improving its performance as an ovarian cancer screening biomarker. We developed and conducted internal and external validation of two prediction models (linear and dichotomous) of circulating CA125 among postmenopausal women using 28,842 controls without ovarian cancer in four large population-based studies. METHODS: We identified controls from three prospective cohort studies, including Prostate, Lung, Colorectal, and Ovarian (PLCO, n=26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n=861), and the Nurses' Health Studies (NHS, n=164) as well as one population-based case-control study, the New England Case Control Study (NEC, n=1,000). CA125 was measured using the CA125II assay in PLCO, NHS, and NEC. Meso Scale Discovery (MSD) platform was used to measure CA125 in EPIC. The MSD assay values were recalibrated to the CA125II scale based on 534 NEC controls with both measurements. CA125 levels were log-transformed to achieve normal distribution or dichotomized by the upper limit of normal (35 U/ml). The prediction models were developed and internally validated using postmenopausal controls in PLCO, and then were externally validated using postmenopausal controls in EPIC, NHS and NEC. The prediction models were developed using stepwise linear or logistic regression with &amp;lt;0.15 as significance level for entry and retention considering factors which have been previously reported to be associated CA125 in postmenopausal women as candidate predictors (age, race, body-mass index (BMI), smoking status and duration, age at menarche, oral contraceptive use, party, age at menopause, time since menopause, hormone replacement therapy (HRT) use and duration, family history of ovarian or breast cancer, previous history of cancer, previous history of benign ovarian cyst, history of endometriosis). We then evaluated the performance of the model in the independent validation datasets. RESULTS: The linear CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, parity, age at menopause, and duration of HRT use as predictors, explaining 5% of the variability of log-transformed CA125 levels. The correlation coefficient of the measured and predicted log-transformed CA125 was 0.18 in the PLCO testing dataset, and showed comparable correlations across the independent validation datasets (0.14-0.16). The dichotomous CA125 prediction model included age, race, BMI, duration of HRT use, and hysterectomy as predictors with an AUC of 0.63 in the PLCO testing dataset and 0.71 in NEC. CONCLUSION: We developed linear and dichotomous circulating CA125 prediction models in postmenopausal women that can form the foundation for creating personalized thresholds of CA125. However, other factors should be considered to increase the predictive capacity of the model. Citation Format: Naoko Sasamoto, Ana Babic, Bernard A. Rosner, Renée T. Fortner, Allison F. Vitonis, Hidemi Yamamoto, Raina N. Fichorova, Daniel W. Cramer, Rudolf Kaaks, Shelley S. Tworoger, Kathryn L. Terry. DEVELOPMENT AND VALIDATION OF CIRCULATING CA125 PREDICTION MODEL IN POSTMENOPAUSAL WOMEN WITHOUT OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-013.

Transvaginal laparoscopic salpingo-oophorectomy: an oncological risk-reducing procedure.

Aim:Since the first natural orifice transluminal endoscopic surgery procedure, renewed interest has arisen in further developing and advancing minimal access surgery. We introduce a natural orifice endoscopic approach for a bilateral salpingo-oophorectomy.Patients & methods:Using the vagina as a natural orifice, we performed a transvaginal laparoscopic salpingo-oophorectomy to remove bilateral adnexa in patients with a strong family history of ovarian and/or breast cancer and those positive for BRCA1/2 mutation.Results:Total 36 women underwent transvaginal laparoscopic salpingo-oophorectomy. Conversion to routine laparoscopy was required in eight patients to complete the operation. No peri-operative complications were noted.Conclusion:We describe a novel approach in gynecological surgery. Our technique proved to be safe and efficient with the advantage of avoiding any abdominal scars.

226O - Prevalence of germline BRCA1 and BRCA2 mutations and variants among ovarian, primary peritoneal and fallopian tube cancer patients: A multicentre Indian study

BackgroundThe worldwide reported prevalence of germline pathogenic BRCA1 and BRCA2 mutations in ovarian cancer patients is 17 % (3-27 %) and that of variants of uncertain significance (VUS) is about 10 %. 1, 2There is deficient data on the prevalence of BRCA mutations in Indian patients. We aimed to estimate the prevalence of germline BRCA mutations among Indian patients with ovarian, primary peritoneal or fallopian tube cancer. MethodsThis was a cross-sectional, multicenter, prospective, observational study conducted at 9 sites from different geographical regions across India which enrolled patients with new or previous diagnosis of ovarian, primary peritoneal, or fallopian tube cancer. Patients underwent blood testing using NGS based platform for germline BRCA. The calculated sample size for this study was 228, assuming 5 % precision around an estimated point prevalence of 15.8 % with a dropout rate of 10 %. ResultsA total of 239 patients were enrolled, of whom 16 were newly diagnosed, treatment naïve, and 223 had a previous diagnosis of ovarian cancer and had received between 1- 9 prior lines of therapy. Germline pathogenic or likely pathogenic BRCA1/BRCA2 mutations were seen in 61 (25.5%, 95% CI 20.12, 31.54) and VUS were seen in 10 (4.2%, 95% CI 2.02 – 7.54) patients, respectively. Among 159 patients with serous histology tumours, 48 (30.2%) had pathogenic/likely pathogenic germline BRCA1/BRCA2 mutations while 16 of 74 (16.2 %) patients with non-serous histology tumours had this finding. Of the 61 patients in this study with germline pathogenic/likely pathogenic BRCA1/BRCA2 mutation, 41 (67.1 %) did not have a family history of breast and/or ovarian cancer. ConclusionsApproximately one-fourth of unselected ovarian cancer patients from India had germline BRCA1/BRCA2 mutations of whom, nearly two-thirds did not have a family history of breast and/or ovarian cancers. Legal entity responsible for the studyAstraZeneca Pharma India Limited. FundingAstraZeneca Pharma India Limited. DisclosureS. Gupta: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. S. Rajappa: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. S.H. Advani: Advisory / Consultancy: AstraZeneca. A. Agarwal: Speaker Bureau / Expert testimony: AstraZeneca. S. Aggarwal: Advisory / Consultancy: AstraZeneca. C. Goswami: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. S. Dattatreya Palanki: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. D. Arya: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. R. Kodagali: Full / Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.

Establishing a Cohort of Transgender Men and Gender Nonconforming Individuals to Understand the Molecular Impact of Testosterone on Breast Physiology.

Purpose: To characterize a cohort of transgender men and masculine-centered gender nonconforming individuals who underwent gender-affirming chest-contouring surgeries at our institution between 2013 and 2018.Methods: Demographics, medical history, and breast histopathological assessment for 340 patients were retrieved from medical records.Results: Most of our patients were white, non-Hispanic (75.0%), were taking testosterone (83.2%), and opted for chest-contouring surgery after 12–14 months of testosterone therapy. Ten patients were parous (2.9%). Seventy-nine (23.2%) and 27 (7.9%) patients had a family history of breast cancer or ovarian cancer, respectively. One transgender man was incidentally diagnosed with ductal carcinoma in situ at chest-contouring surgery.Conclusion: Future studies on this cohort will provide valuable insights about the impact of testosterone on breast physiology.