History Of Ovarian Cancer Research Articles

A RARE CASE OF PROTRACTED ANAPHYLAXIS CAUSED BY ACETAMINOPHEN

<h3>Introduction</h3> Acetaminophen is a rare but recognized etiology of anaphylaxis. We present an unusual case of protracted anaphylaxis requiring intensive care unit (ICU) monitoring following intravenous (IV) acetaminophen. <h3>Case Description</h3> A 49-year-old female with a history of ovarian cancer presented to the emergency department with pruritic urticarial rash, fevers, tachycardia, and relative hypotension. A sepsis workup was initiated. Hemodynamics improved with broad-spectrum antibiotics and fluids. Due to symptomatic high-grade fevers, IV acetaminophen was administered. Her rash, tachycardia, and relative hypotension worsened one hour following infusion. Despite resuscitation with diphenhydramine and fluids, she remained tachycardic and febrile, prompting treatment for suspected anaphylaxis with intramuscular epinephrine, corticosteroids, and additional diphenhydramine. Her rash and hemodynamics improved moderately. She was subsequently started on norepinephrine and transferred to the medical ICU, where she had two days of persistent tachycardia and fluctuating urticarial rash responsive to antihistamines. Infectious workup was unrevealing. She later revealed a prior history of urticaria following home oral acetaminophen. Tryptase drawn one hour after decompensation was elevated to 23.8 mcg/L (baseline 3.2 mcg/L). The diagnosis was made of IgE-mediated reaction to acetaminophen causing protracted anaphylaxis. <h3>Discussion</h3> Anaphylaxis secondary to acetaminophen is an uncommon but recognized phenomenon. An initial differential included pseudoallergic reaction, given acetaminophen can be a weak cyclooxygenase-1 inhibitor causing direct mast cell activation and urticaria; however, this does not classically cause hypotension. Overall, this presentation may represent a mixed picture of sepsis of unclear etiology with superimposed IgE-mediated reaction. It is important to recognize anaphylaxis can co-exist with sepsis and manifest with overlapping symptoms.

A combined clinical and genetic model for predicting risk of ovarian cancer.

Women with a family history of ovarian cancer or a pathogenic or likely pathogenic gene variant are at high risk of the disease, but very few women have these risk factors. We assessed whether a combined polygenic and clinical risk score could predict risk of ovarian cancer in population-based women who would otherwise be considered as being at average risk. We used the UK Biobank to conduct a prospective cohort study assessing the performance of 10-year ovarian cancer risks based on a polygenic risk score, a clinical risk score and a combined risk score. We used Cox regression to assess association, Harrell's C-index to assess discrimination and Poisson regression to assess calibration. The combined risk model performed best and problems with calibration were overcome by recalibrating the model, which then had a hazard ratio per quintile of risk of 1.338 [95% confidence interval (CI), 1.152-1.553], a Harrell's C-index of 0.663 (95% CI, 0.629-0.698) and overall calibration of 1.000 (95% CI, 0.874-1.145). In the refined model with estimates based on the entire dataset, women in the top quintile of 10-year risk were at 1.387 (95% CI, 1.086-1.688) times increased risk, while women in the top quintile of full-lifetime risk were at 1.527 (95% CI, 1.187-1.866) times increased risk compared with the population. Identification of women who are at high risk of ovarian cancer can allow healthcare providers and patients to engage in joint decision-making discussions around the risks and benefits of screening options or risk-reducing surgery.

Carcinoma Ovary with Lung Metastasis: A Rare Case Report

Ovarian cancer is the most lethal gynecological malignancy. Despite advances in chemotherapy, five year survival rate of advanced ovarian cancer patients with peritoneal metastasis remains around 30%. The most significant prognostic factor is stage and most patients present at an advanced stage with peritoneal dissemination. There is often no clearly identifiable precursor lesion, therefore, the events leading to metastatic disease are poorly understood. Solitary lung metastasis is extremely rare. We report the case of a 39-year-old woman who was admitted to our department with a lung mass. She had a past history of ovarian cancer 6years ago for which she underwent Cytoreductive surgery and HIPEC in august 2016. Histopathology report suggestive of High-grade serous carcinoma. She received adjuvant chemotherapy. She was on follow up and PET scan shows two soft tissue density nodules noted in left lung lower lobe largest 2.8×2.5cm. Left lower lobectomy was performed. Microscopically, the tumor was a high-grade serous carcinoma and was diagnosed as an ovarian cancer metastasis.

Efficacy of minodronic acid for the prevention of osteoporosis in premenopausal women with gynaecologic disease who undergo bilateral oophorectomy: a single-centre, non-randomised controlled, experimental study

We evaluated the efficacy of minodronic acid for osteoporosis prevention after bilateral oophorectomy for gynaecologic disease in premenopausal women. Bone mineral density (BMD) and young adult mean (YAM) data from the lumbar vertebrae and femur and bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5 b (TRACP 5 b) data were obtained for 101 patients. The primary endpoint was the efficacy of minodronic acid for osteoporosis prevention. Fifty-five and 31 patients were assigned to medication and no medication groups, respectively. The decrease in BMD and YAM and the increase in BAP/TRACP-5b were significantly more suppressed in the medication group. There were no significant between-group differences in age at oophorectomy, cancer type, body mass index (BMI), and adjuvant therapy. There were no adverse events due to minodronic acid. Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy. Impact statement What is already known on this subject? Although the current strategy for osteoporosis prevention after premenopausal bilateral oophorectomy (b-OVX) is hormone therapy (HT), there is no consensus on the treatment duration or adverse events. What do the results of this study add? Therefore, we planned a prospective study to evaluate the efficacy of prophylactic treatment for osteoporosis after b-OVX in premenopausal women with gynaecologic disease using minodronic acid, an oral bisphosphonate, which have a strong evidence of the treatment for osteoporosis. The result showed minodronic acid significantly suppressed the decrease in bone mineral density (BMD) and young adult mean (YAM) and the increase in bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5b (TRACP 5b). Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy. What are the implications of these findings for clinical practice and/or further research? Minodronic acid treatment for osteoporosis prevention after premenopausal b-OVX may be effective as a therapeutic agent after the cessation of HT, or alternative for patients who are contraindicated for HT in breast cancer and thrombosis and should be administered with caution with a history of uterine or ovarian cancer.

Evaluation of risk factors and effective factors in determining the prognosis of ovarian cancer

Ovarian cancer is still one of the leading causes of death from reproductive system cancers. Despite recent advances in treating this cancer, ovarian cancer is the fourth cause of death in women. Knowing the risk factors of ovarian cancer and the factors affecting the prognosis of this tumor can be helpful. This study investigates risk factors and practical factors in determining the prognosis of ovarian cancer. In the present study, we searched through various databases such as Wiley Online Library, Google Scholar, PubMed, and Elsevier with the keywords Polycystic Ovarian, Ovarian Estrogen-Dependent Tumors Syndrome Chronic Inflammation, Prognosis of Ovarian Cancer, among published articles from 1996 to 2022. Based on these studies, we investigated the age of menstruation, age of menopause, number of pregnancies, family history of ovarian cancer and genital tract cancer, use of birth control pills, histological type of tumor, degree of cell differentiation, type of surgery, and post-surgery treatments, and examination of the serum level of tumor marker CA12, as well as the role of polycystic ovary syndrome in the development of ovarian cancer. In general, infertility was one of the most important risk factors and the serum level of tumor marker CA125 was one of the most important determinants of ovarian cancer prognosis.

Follicular lymphoma without lymphadenopathy incidentally diagnosed by sentinel lymph node biopsy during breast cancer surgery: a case report

BackgroundConcurrent breast cancer and malignant lymphoma is a rare phenomenon. This report describes malignant lymphoma that was incidentally diagnosed from a sentinel lymph node biopsy (SLNB) during breast cancer surgery.Case presentationA 73-year-old woman with a history of ovarian cancer and diabetes presented with right focal asymmetric density on a mammogram acquired during routine breast cancer screening. Ultrasonography (US) and magnetic resonance imaging (MRI) showed a 13.5-mm tumor in the upper lateral region of the right breast. A US-guided Mammotome biopsy revealed invasive ductal carcinoma of the right breast. Preoperative assessments including positron emission tomography–computerized tomography, found no evidence of axillary lymphadenopathy or distant metastasis. Because the breast cancer was stage I, the patient underwent a right mastectomy and a sentinel lymph node biopsy (SLNB) at our hospital. Pathological assessment of the biopsy revealed follicular lymphoma (FL), but no metastatic breast cancer. The patient was referred to hematology to stage the FL. Bone marrow findings were negative and stage I FL was diagnosed. After the mastectomy, she was monitored and given adjuvant therapy with an aromatase inhibitor.ConclusionsFollicular lymphoma was incidentally diagnosed from an SLNB obtained to determine the dissemination of early-stage breast cancer. Collaboration with hematologists is important to determine optimal treatment plans for such patients regardless of the rarity of such events.

Outcomes of Pregnancies and Deliveries of Patients Who Underwent Fertility-Preserving Surgery for Early-Stage Epithelial Ovarian Cancer.

Some studies have shown increased risks of preterm birth, low birth weight, and cesarean delivery after oncologic treatment; others have shown the opposite. We evaluated the outcomes of pregnancies and deliveries of patients who underwent fertility-preserving surgery (FSS) for early-stage epithelial ovarian cancer (EOC) and examined their perinatal prognosis. This retrospective study included women with a history of stage IA or IC ovarian cancer reported in our previous study. The primary outcome was preterm birth after cancer diagnosis was considered. Secondary outcomes were neonatal morbidity and severe maternal morbidity. Thirty-one children were born to 25 women who had undergone FSS. The mean number of weeks at delivery was 38.7 ± 0.7, and the mean birth weight of infants was 3021 ± 160 g. With respect to pregnancy outcomes, 5 patients had preterm labor and 26 had full-term labor. The delivery mode was vaginal delivery in 18 patients and cesarean delivery in 13. Complications during pregnancy included placenta previa (one case) and pelvic abscess (one case). Except for three preterm infants with low birth weight, there were no other perinatal abnormalities. Pregnancy after fertility preservation in EOC has an excellent perinatal prognosis, although the cesarean delivery rate is high.

Prevalence of BRCA1 and BRCA2 pathogenic variants in 8627 unselected patients with breast cancer: stratification of age at diagnosis, family history and molecular subtype.

Comprehensively analyzing the prevalence of BRCA1/2 germline pathogenic variants (PVs) in a large cohort of unselected Chinese patients with breast cancer has great clinical importance. Germline pathogenic variants in full-length BRCA1/2 genes were determined through next-generation sequencing and/or Sanger sequencing assays in 8627 unselected Chinese patients with breast cancer who were treated at the Breast Center of Peking University Cancer Hospital. The prevalence of BRCA1/2 PVs was further stratified by age at diagnosis, family history of cancer and molecular subtype. We found that the overall prevalence of BRCA1/2 PVs was 6.0% in the entire cohort, 2.4% in BRCA1 and 3.7% in BRCA2. The prevalence of BRCA1/2 PVs in patients with early-onset breast cancer (age at diagnosis ≤ 40years) was significantly higher than that in patients over the age of 40 (9.7% vs. 5.1%). The prevalence rates of BRCA1/2 PVs in patients with a family history of breast, ovarian, pancreatic, and prostate cancer were 19.5%, 39.0%, 11.1%, and 12.8%, respectively. Moreover, the number of relatives affected by breast cancer was associated with a higher prevalence of BRCA1/2 PVs. Molecular subtypes were associated with the prevalence of BRCA1/2 PVs. Patients with the triple-negative phenotype had the highest prevalence of BRCA1/2 PVs (13.3%) among the three molecular groups, followed by the HR + and HER2- group (5.9%), and the lowest was in the HER2 + group (2.5%). Our study provides the most comprehensive information to date on the prevalence of BRCA1/2 PVs in unselected Chinese patients with breast cancer.

Ventral incisional hernia with herniation of the left hepatic lobe: A case report

Incisional hernias are a very common complication of abdominal surgery, reaching form 5–20% to around 69% in the case of high-risk patients with prospective long-term follow-up. Herniation of the liver, however, is extremely rare and there are only a handful of cases reported. Here we present a case concerning a complex incisional defect of the abdominal wall involving liver herniation with mild ischemia that required extensive surgery to repair in a patient with previous history of ovarian cancer with incomplete resection surgery. The treatment choice was manual reduction of the hernia at the moment of presentation and delayed elective surgery for definite correction, aiming at full functional recovery of the abdominal wall muscles and to a better outcome regarding quality of life when compared to mesh repair without closure of the defect. As hernias involving left hepatic lobe are rare and mostly occur in patients with comorbidities, conservative management should be considered. However, depending on the effect they have in quality of life, preoperative conditions should be optimized aiming for a successful abdominal wall reconstruction, despite the patient’s comorbidities.

Guideline concordance for risk-reducing bilateral salpingo- oophorectomy in a cohort of reproductive age women with BRCA1/2 mutations (562)

<b>Objectives:</b> Current guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRSO) for women diagnosed with <i>BRCA1</i> mutations by ages 35-40 and <i>BRCA2</i> mutations by ages 40-45. Our study aimed to examine guideline concordance for RRSO in a cohort of women with <i>BRCA1</i> and <i>BRCA2</i> mutations. <b>Methods:</b> We performed a retrospective cohort study of women aged 18-45 diagnosed with pathogenic <i>BRCA1</i> or <i>BRCA2</i> mutations seen by gynecologic oncologists at a single academic center between 2015 and 2019 and were eligible for RRSO per national guidelines. Our primary outcome was guideline concordance, defined as <i>1)</i> electing RRSO by age 35 for women with <i>BRCA1</i> and by age 40 for women with <i>BRCA2,</i> or <i>2)</i> if the patient was diagnosed after age 35 with <i>BRCA1</i> or after age 40 with <i>BRCA2,</i> electing RRSO within one year of diagnosis. Patients were monitored for electing RRSO by July 1^st, 2021. We excluded those previously diagnosed with gynecologic malignancies and those whose current age was less than 35 for <i>BRCA1</i> and less than 40 for <i>BRCA2</i>. We examined patient differences in guideline concordance using Fisher's exact and Pearson's Chisquare tests. We then identified relevant patient factors associated with guideline concordance using univariate log-binomial regression. <b>Results:</b> Of 62 total patients, 41 had a diagnosis of a suspected pathogenic or pathogenic <i>BRCA1</i> mutation (median age at diagnosis 34 y), and 21 had a diagnosis of suspected pathogenic or pathogenic <i>BRCA2</i> mutation (median age at diagnosis 41 y). Overall, 23% of patients (<i>n</i>=14/62) were guideline-concordant, or 27% of <i>BRCA1</i> patients (<i>n</i>=11/41) and 14% of <i>BRCA2</i> patients (<i>n</i>=3/21). In the descriptive analysis, guideline concordance was more common in non-White women compared to White women (<i>n</i>=7/18 vs <i>n</i>=7/44, p=0.09) and single women compared to partnered women (<i>n</i>=4/8 vs <i>n</i>=10/54, p=0.07). More women with a family history of both breast and ovarian cancer were guideline-concordant than women with a family history of breast cancer only (<i>n</i>=9/27 vs <i>n</i>=5/30, p=0.14). However, women with a personal history of breast cancer were less commonly guideline-concordant than women without a personal history (<i>n</i>=3/19 vs <i>n</i>=11/43, p=0.5). In univariate analysis, factors significantly associated with guideline concordance were non-White compared to White race (RR: 2.4, 95% CI: 1.00-5.97) and being single compared to being partnered (RR: 2.7, 95% CI: 1.11-6.58). There were no significant associations with guideline concordance by patient BMI, having children, having private insurance, income, type of <i>BRCA</i> diagnosis, past diagnosis of breast cancer, or family history of breast or ovarian cancer. Table 1 <b>Conclusions:</b> A minority of reproductive-age <i>BRCA1/2</i> patients met guideline concordance for electing RRSO. Being guideline-concordant was associated with non-White and single status. Further studies are needed to verify and identify disparities in meeting guideline- recommended timing of RRSO for the <i>BRCA1/BRCA2</i> population.

Disparities in Oncofertility: Assisted reproductive technology utilization and fertility-sparing oncology care in women with a history of breast, ovarian, cervical or endometrial cancer (094)

Disparities in Oncofertility: Assisted reproductive technology utilization and fertility-sparing oncology care in women with a history of breast, ovarian, cervical or endometrial cancer (094)

Factors associated with concurrent vs. sequentially combined surgery for patients undergoing risk-reducing bilateral salpingo- oophorectomy (434)

Factors associated with concurrent vs. sequentially combined surgery for patients undergoing risk-reducing bilateral salpingo- oophorectomy (434)

Trends in concurrent hysterectomy or endometrial sampling at the time of bilateral salpingo-oophorectomy for risk-reducing or therapeutic indications (386)

Trends in concurrent hysterectomy or endometrial sampling at the time of bilateral salpingo-oophorectomy for risk-reducing or therapeutic indications (386)

Malignant Bowel Obstruction in Ovarian Cancer Recurrence: The Role of Palliative Surgery in a Decision-Making Process

Background: Malignant bowel obstruction (MBO) is often the latest stage in ovarian cancer (OC). The therapy of this condition ranges from medical waiting to surgery. The objective of this pilot study is to compare the two strategies so that we can provide a path forward for future studies. Methods: From 700 women diagnosed with OC in the database of the Division of Gynecologic Oncology we crossed the names of those admitted by the emergency services of the IRCSS Azienda Ospedaliero Universitaria of Bologna, Italy. We selected MBO patients with a history of OC as the only neoplastic condition and compared the results between medical conduct and surgery to restore intestinal transit. Results: Of the 700 women in our database, 36 were eligible for study according to the inclusion and exclusion criteria: 9 in surgery group and 27 in medical group. Surgical conduct (tumor biopsy and stoma) appears to be resolutory for the obstruction and have a better result than medical therapy regarding recurrence of MBO, despite the development of greater complications. Relapses of MBOs occurred in 11% of surgical patients and 44% of medical patients (p = 0.0714). Furthermore, after surgical treatment, five patients (55%) experienced postoperative complications; in four cases, severe anemia requiring blood transfusion, while one patient developed post-surgical sepsis, which evolved into multiple organ failure and death. Of the 9 patients treated surgically, 2 (22%) were given surgery as a first choice. In most cases (78%), surgery was decided upon when medical treatment failed. The only discriminative factor appears to be age. The length of hospitalization increased with the patient’s age (p = 0.0181) as statistically significant factors for a worse outcome in surgery. Conclusions: MBO requires complex and multidisciplinary management where different factors need to be considered before initiating surgical therapy. Future studies are needed to deal with this complex problem.

Ovarian cancer risk of Chinese women with BRCA1/2 germline pathogenic variants

Estimating the lifetime risk of ovarian cancer in Chinese women with BRCA1/2 germline pathogenic variants (PVs) is of great importance for the clinical management of BRCA1/2 carriers. This cohort study recruited 9903 unselected Chinese breast cancer patients whose BRCA1/2 status was determined. Of these, 3984 probands completed family history questionnaires, which investigated the health status of their relatives, including 11,997 female first-degree relatives. The ovarian cancer risk of BRCA1/2 germline pathogenic carriers was estimated using the ovarian cancer history of proband first-degree female relatives via the Kin-cohort method. Of the 3984 probands, 126 (3.2%) carried BRCA1 PVs, and 183 (4.6%) carried BRCA2 PVs. The estimated cumulative risks of ovarian cancer by age 70 were 15.3% (95% CI 8.4-18.6%) for BRCA1 carriers, 5.5% (95% CI 2.0-10.2%) for BRCA2 carriers, and 0.4% (95% CI 0.3-0.7%) for noncarriers. The cumulative risks of ovarian cancer were very low before the age of 40 for both BRCA1 and BRCA2 carriers and were an increase up to age 45. The cumulative ovarian cancer risk of BRCA1 carriers was approximately three times higher than that of BRCA2 carriers, and BRCA1 and BRCA2 carriers had 38- and 14-fold higher risks than non-BRCA carriers, respectively. The findings indicate that Chinese women with BRCA1/2 PVs have high risks of ovarian cancer in their lifetime, especially BRCA1 carriers. These results are useful for devising optimal strategies to reduce ovarian cancer risk in BRCA1/2 carriers.

Patient and Clinician Decision Support to Increase Genetic Counseling for Hereditary Breast and Ovarian Cancer Syndrome in Primary Care

To promote the identification of women carrying BRCA1/2 variants, the US Preventive Services Task Force recommends that primary care clinicians screen asymptomatic women for an increased risk of carrying a BRCA1/2 variant risk. To examine the effects of patient and clinician decision support about BRCA1/2 genetic testing compared with standard education alone. This clustered randomized clinical trial was conducted at an academic medical center including 67 clinicians (unit of randomization) and 187 patients. Patient eligibility criteria included women aged 21 to 75 years with no history of breast or ovarian cancer, no prior genetic counseling or testing for hereditary breast and ovarian cancer syndrome (HBOC), and meeting family history criteria for BRCA1/2 genetic testing. RealRisks decision aid for patients and the Breast Cancer Risk Navigation Tool decision support for clinicians. Patients scheduled a visit with their clinician within 6 months of enrollment. The primary end point was genetic counseling uptake at 6 months. Secondary outcomes were genetic testing uptake at 6 and 24 months, decision-making measures (perceived breast cancer risk, breast cancer worry, genetic testing knowledge, decision conflict) based upon patient surveys administered at baseline, 1 month, postclinic visit, and 6 months. From December 2018 to February 2020, 187 evaluable patients (101 in the intervention group, 86 in the control group) were enrolled (mean [SD] age: 40.7 [13.2] years; 88 Hispanic patients [46.6%]; 15 non-Hispanic Black patients [8.1%]; 72 non-Hispanic White patients [38.9%]; 35 patients [18.9%] with high school education or less) and 164 (87.8%) completed the trial. There was no significant difference in genetic counseling uptake at 6 months between the intervention group (20 patients [19.8%]) and control group (10 patients [11.6%]; difference, 8.2 percentage points; OR, 1.88 [95% CI, 0.82-4.30]; P = .14). Genetic testing uptake within 6 months was also statistically nonsignificant (13 patients [12.9%] in the intervention group vs 7 patients [8.1%] in the control group; P = .31). At 24 months, genetic testing uptake was 31 patients (30.7%) in intervention vs 18 patients (20.9%) in control (P = .14). Comparing decision-making measures between groups at baseline to 6 months, there were significant decreases in perceived breast cancer risk and in breast cancer worry (standard mean differences = -0.48 and -0.40, respectively). This randomized clinical trial did not find a significant increase in genetic counseling uptake among patients who received patient and clinician decision support vs those who received standard education, although more than one-third of the ethnically diverse women enrolled in the intervention underwent genetic counseling. These findings suggest that the main advantage for these high-risk women is the ability to opt for screening and preventive services to decrease their cancer risk. ClinicalTrials.gov Identifier: NCT03470402.

Male breast cancer: a 20-year multicenter experience

Aim: Male breast cancer (MBC) is a rare disease and accounts for approximately 1% of breast cancer. Treatment is largely extrapolated from female breast cancer due to lack of data in MBC. However, there are distinct features of MBC that warrant different treatment approach. We aim to better characterize the risk factors, clinicopathologic features, treatment and outcome of MBC patients from six hospitals across Steward Healthcare Network. Materials &amp; methods: A total of 107 men with breast cancer were identified from the respective cancer registry at Steward and 64 patients were included with complete medical records. Their clinical, histopathological and treatment records were retrospectively reviewed. Kaplan–Meier method was used to determine the 5, 10 year overall survival (OS) rate and relapse free survival rate and Cox Regression test was used to assess the association between patient outcome and age at diagnosis, metastasis status at time of diagnosis, tumor size, nodal involvement and use of chemotherapy. Results: Of these 64 patients, median age at diagnosis was 68 years, majority of patients were white, 13 patients had family history of breast or ovarian cancer (20.3%), four patients tested positive for BRCA2 (6.25). Majority of patients presented painless breast lump. A total of 59 patients (92.2%) had invasive ductal carcinoma, and 31 patients (48.4%) had lymph node involvement at time of diagnosis. A total of 62 patients (96.8%) had M0 disease at time of diagnosis. About 97% of patients had estrogen receptor (ER) positive cancer. Most patients underwent mastectomy (87.5%), 35 patients (54.6%) received adjuvant radiation therapy, 19 patients (30%) received adjuvant chemotherapy and 96.7% of patients received adjuvant hormonal therapy. The median follow-up was 71.5 months (range 6–250 months), 5-year survival rate was 86.9% (95% CI: 74.5–93.6%), 5-year relapse free survival rate was 89.9% (95% CI: 77.4–95.7%) and 10-year survival rate was 58.1% (95% CI: 41.0–71.8%). The presence of distant metastasis at the time of initial diagnosis was the only factor associated with shorter OS (hazard ratio: 22.54, p &lt; 0.0001). Conclusion: Majority of MBC patients present with palpable breast mass and the tumors are almost exclusively hormone receptor positive. Majority of patients present without distant metastasis and received surgical therapy; however, only a small subset of patients received breast conserving surgery for T1 tumor. Almost all patients received adjuvant hormonal therapy. OS and relapse free survival in our cohort is similar to historic reports in female breast cancer.

Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer.

Simple SummaryMale breast cancer (mBC) is a rare disease associated with a high prevalence of pathogenic germline variants (PVs) in the BRCA2 gene. However, data regarding other breast cancer (BC) predisposition genes are limited or conflicting. We investigated the prevalence of PVs in BRCA1/2 and 23 other cancer predisposition genes using an overall study sample of 614 patients with mBC. A high proportion of patients with mBC carried pathogenic germline variants in BRCA2 (23.0%, 142/614) and BRCA1 (4.6%, 28/614). A BRCA1/2 PV prevalence of 11.0% was identified in patients with mBC without a family history of breast and/or ovarian cancer. Patients with BRCA1/2 PVs did not show an earlier disease onset than those without. Case-control analyses revealed significant associations of protein-truncating variants in BRCA1, BRCA2, CHEK2, PALB2, and ATM with mBC. Our findings support the benefit of multi-gene panel testing in patients with mBC.Male breast cancer (mBC) is associated with a high prevalence of pathogenic variants (PVs) in the BRCA2 gene; however, data regarding other BC predisposition genes are limited. In this retrospective multicenter study, we investigated the prevalence of PVs in BRCA1/2 and 23 non-BRCA1/2 genes using a sample of 614 patients with mBC, recruited through the centers of the German Consortium for Hereditary Breast and Ovarian Cancer. A high proportion of patients with mBC carried PVs in BRCA2 (23.0%, 142/614) and BRCA1 (4.6%, 28/614). The prevalence of BRCA1/2 PVs was 11.0% in patients with mBC without a family history of breast and/or ovarian cancer. Patients with BRCA1/2 PVs did not show an earlier disease onset than those without. The predominant clinical presentation of tumor phenotypes was estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, and HER2-negative (77.7%); further, 10.2% of the tumors were triple-positive, and 1.2% were triple-negative. No association was found between ER/PR/HER2 status and BRCA1/2 PV occurrence. Comparing the prevalence of protein-truncating variants (PTVs) between patients with mBC and control data (ExAC, n = 27,173) revealed significant associations of PTVs in both BRCA1 and BRCA2 with mBC (BRCA1: OR = 17.04, 95% CI = 10.54–26.82, p < 10−5; BRCA2: OR = 77.71, 95% CI = 58.71–102.33, p < 10−5). A case-control investigation of 23 non-BRCA1/2 genes in 340 BRCA1/2-negative patients and ExAC controls revealed significant associations of PTVs in CHEK2, PALB2, and ATM with mBC (CHEK2: OR = 3.78, 95% CI = 1.59–7.71, p = 0.002; PALB2: OR = 14.77, 95% CI = 5.02–36.02, p < 10−5; ATM: OR = 3.36, 95% CI = 0.89–8.96, p = 0.04). Overall, our findings support the benefit of multi-gene panel testing in patients with mBC irrespective of their family history, age at disease onset, and tumor phenotype.

Understanding Cancer Genetic Risk Assessment Intentions in a Tailored Risk Communication Intervention Randomized Controlled Trial

Background: Pathogenic variants in cancer predisposition genes increase second, hereditary cancer risk among women with breast and/or ovarian cancer, and primary cancers in their relatives. National guidelines recommend cancer genetic risk assessment (CGRA) (genetic counseling and/or genetic testing) for women at increased hereditary breast and ovarian cancer (HBOC) risk. Yet, less than half of high risk women, including rural dwellers and racial minorities have accessed CGRA. Purpose: The Genetic Risk Assessment for Cancer Education and Empowerment Project (GRACE), a superiority trial, addressed this translational gap, testing the efficacy of a targeted print brochure (TP) vs tailored counseling and navigation (TCN) vs usual care (UC) on CGRA intentions. TCN targeted behavioral variables theorized to mediate CGRA intentions. We believe GRACE is the first study of its kind promoting guideline-based CGRA to women at increased HBOC risk. Methods: CGRA-eligible women were recruited from three state cancer registries (N=641), completed a baseline survey, and randomized to TCN, TP or UC. TP and TCN received the mailed educational brochure. TCN also engaged in a telephone-based decision coaching and navigation session using motivational interviewing and tailored materials based on the Extended Parallel Process Model and Health Action Process Approach. Participants completed a follow-up survey at one month. Results: TCN improved CGRA intentions compared to TP (0.64, p&amp;lt;0.001, CI 0.32, 0.97) and UC (0.69, p&amp;lt;0.001, CI 0.37, 1.02). Theoretical targets, perceived risk (0.77, p=0.02, CI 0.11, 1.44) and self-efficacy (0.67, p=0.04, CI 0.05, 1.28) mediated CGRA intentions in TCN. Stratification showed increases in CGRA intentions for TCN vs TP among non-Hispanic Whites, Hispanics, urban dwellers, and women with low health literacy and no family history of breast and/or ovarian cancer (FBOC). In TCN, perceived self-efficacy improved in women with no FBOC. Conclusions: Improvements in CGRA intentions and theorized mediators support use of tailored risk communication interventions in Hispanics and women with low health literacy and no FBOC. Further tailoring may improve CGRA intentions in Blacks, other minorities, rural dwellers, and women with high health literacy and FBOC.

Abstract 1451: BRCA1 and BRCA2 germline mutational spectrum in Algerian triple negative breast cancer (TNBC) patients

Abstract Background: Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. To date, triple negative breast cancer (TNBC) shows substantial overlap with basal type cancer and it is associated with aggressive tumor behavior, poor prognosis and BRCA1 mutations. In the present study, we screened for the prevalence of BRCA1 and BRCA2 germline mutations in a cohort of 169 TNBC patients using PCR-Sanger sequencing and NGS with a cancer panel of 30 hereditary cancer genes or BRCA1/BRCA2 genetic test. Materials and Methods: 169 TNBC patients and their relatives were referred trough several public hospitals from six years (2013-2019). BRCA1 germline mutation was screened using PCR-Sanger sequencing in 66 TNBC patients with strong family history of breast and ovarian cancer and 103 sporadic TNBC patients including all exons where a mutation was previously found in Algerian population (exons 2, 3, 4, 10, 17 and 19). BRCA2 germline mutation was screened using PCR-Sanger sequencing in 24 TNBC patients with strong family history of breast cancer including all exons where a mutation was previously found in Algerian patients (exons 10 and 22). In addition, nine (9) TNBC patients with strong family history of breast and ovarian cancer were analyzed by NGS using BRCA1 and BRCA2 test or a cancer panel of 30 hereditary genes (Colors genomics). Results: The analysis of the genomic DNA samples of 169 TNBC patients revealed that 15 patients carried pathogenic germline variants in BRCA1 gene and three patients carried pathogenic variants in BRCA2 gene (10.65%). Eight distinct germline mutations in BRCA1 have been detected in this study: c.83_84delTG, c.181T&amp;gt;G, c.798_799delTT, c.505C&amp;gt;T, c.923_924delGC, c.2125_2126insA, c.5257A&amp;gt;G and deletion of exon 15. Interestingly, the recurrent and specific mutation c.83_84delTG has been detected in 4 unrelated TNBC patients. The pathogenic variant c.2125_2126insA has been detected in three unrelated families and also in the first relatives of 2 patients. The rare likely pathogenic variant BRCA1 c.5257A&amp;gt;G/p.Arg1753Gly has been detected in young female TNBC patient. The Del exon 15 in BRCA1 has been detected in two unrelated patients. Three distinct germline mutations in BRCA2 have been detected in three TNBC patients: c.1813dupA, c.7654dupA and c.8485C&amp;gt;T. Interestingly, these three mutations are reported for the first time in Algerian population. The c.1813dupA and c.8485C&amp;gt;T pathogenic variants have been detected in two young female TNBC patients with a family history of male breast cancer. Conclusions: In the current study, we detected recurrent germline mutations in BRCA1 gene in early onset TNBC patients. BRCA2 pathogenic variants have also been detected in young female TNBC patients. TNBC immunophenotype should be considered as an additional criterion for genetic counselling and testing of BRCA genes in Algerian women with early onset breast cancer. Citation Format: Farid Cherbal, Chiraz Mehemmai, Hadjer Gaceb, Hassen Mahfouf, Kada Boualga. BRCA1 and BRCA2 germline mutational spectrum in Algerian triple negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1451.