Ovarian cancer is a heterogeneous disease that encompasses a number of different cellular subtypes, the most common of which is high-grade serous ovarian cancer (HGSOC). Still today, ovarian cancer is primarily treated with chemotherapy and surgery. Recent advances in the hereditary understanding of this disease have shown a significant role for the BRCA gene. While only a minority of patients with HGSOC will have a germline BRCA mutation, many others may have tumor genetic aberrations within BRCA or other homologous recombination proteins. Genetic screening for these BRCA mutations has allowed improved preventative measures and therapeutic development. This review focuses on the understanding of BRCA mutations and their relationship with ovarian cancer development, as well as future therapeutic targets.

Lymphedema remains a poorly understood entity that can occur after lymphadenectomy. Herein, we will review the pathogenesis of lymphedema, diagnostic modalities and the natural history of extremity involvement. We will review the incidence of upper extremity lymphedema in patients treated for breast malignancies and lower extremity lymphedema in those treated for gynecologic malignancy. Finally, we will review traditional treatment modalities for lymphedema, as well as introduce new surgical treatment modalities that are under active investigation.

This publication represents an extensive literature review with the goal of providing guidelines for the evaluation and management of cervical adenocarcinoma in situ (AIS). The authors drafted the guidelines on behalf of the Society of Gynecologic Oncology, and the guidelines have been reviewed and endorsed by the ASCCP. These guidelines harmonize with the ASCCP Risk-Based Management Consensus Guidelines and provide more specific guidance beyond that provided by the ASCCP guidelines. Examples of updates include recommendations to optimize the diagnostic excisional specimen, AIS management in the setting of positive compared with negative margins on the excisional specimen, surveillance and definitive management after fertility-sparing treatment, and management of AIS in pregnancy. The increasing incidence of AIS, its association with human papillomavirus-18 infection, challenges in diagnosis owing to frequent origin within the endocervical canal, and the possibility of skip lesions all make AIS a unique diagnosis whose management needs to be differentiated from the management of the more prevalent squamous cell dysplasia.

•Extreme obesity may preclude patients from primary surgical management of endometrial cancer.•Bariatric surgery is a safe and effective method of rapid weight loss in patients with extreme obesity.•Delayed hysterectomy, after weight loss from bariatric surgery, is an option in select patients with endometrial cancer.

Purpose

To evaluate the feasibility of implementing systematic patient symptom monitoring during treatment using a smartphone.

Methods

Endometrial [n = 50], ovarian [n = 70] and breast [n = 193] cancer patients participated in text-based symptom reporting for up to 12 months. In order to promote equity, patients without a smartphone were provided with a device, with the phone charges paid by program funds. Each month, patients completed the Patient Health Questionnaire (PHQ-9), and 4 single items assessing fatigue, sleep quality, pain, and global quality of life during the past 7 days rated on a 0 (low) -10 (high) scale. Patients' responses were captured using REDCap, with oncologists receiving monthly feedback. Lay navigators provided assistance to patients with non-medical needs.

Results

Patients utilizing this voluntary program had an overall mean age of 60.5 (range 26-87), and 85% were non-Hispanic white. iPhones were provided to 42 patients, and navigation services were used by 69 patients. Average adherence with monthly surveys ranged between 75-77%, with breast patients having lower adherence after 5 months. The most commonly reported symptoms across cancer types were moderate levels (scores of 4-7) of fatigue and sleep disturbance. At 6 months, 71-77% of all patients believed the surveys were useful to them and their health care team.

Conclusions

We established the feasibility of initiating and managing patients in a monthly text-based symptom-monitoring program. The provision of smartphones and patient navigation were unique and vital components of this program.

Objective

To determine the effect of age on completion of and toxicities following treatment of local regionally advanced cervical cancer (LACC) on Gynecologic Oncology Group (GOG) Phase I-III trials.

Methods

An ancillary data analysis of GOG protocols 113, 120, 165, 219 data was performed. Wilcoxon, Pearson, and Kruskal-Wallis tests were used for univariate and multivariate analysis. Log rank tests were used to compare survival lengths.

Results

One-thousand-three-hundred-nineteen women were included; 60.7% were Caucasian, 15% were age 60-70years and an additional 5% were >70; 87% had squamous histology, 55% had stage IIB disease and 34% had IIIB disease. Performance status declined with age (p=0.006). Histology and tumor stage did not significantly differ. Number of cycles of chemotherapy received, radiation treatment time, nor dose modifications varied with age. Notably, radiation protocol deviations and failure to complete brachytherapy (BT) did increase with age (p=0.022 and p<0.001 respectively). Only all grade lymphatic (p=0.006) and grade≥3 cardiovascular toxicities (p=0.019) were found to vary with age. A 2% increase in the risk of death for every year increase >50 for all-cause mortality (HR 1.02; 95% CI, 1.01-1.04) was found, but no association between age and disease specific mortality was found.

Conclusion

This represents a large analysis of patients treated for LACC with chemo/radiation, approximately 20% of whom were >60years of age. Older patients, had higher rates of incomplete brachytherapy which is not explained by collected toxicity data. Age did not adversely impact completion of chemotherapy and radiation or toxicities.

Background

Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.

Methods

We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models.

Results

Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m² increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (P_interaction < 0.05).

Conclusion

Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

Purpose

We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.

Methods

Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.

Results

The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10^-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10^-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10^-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10^-12) carriers. The associations in the prospective cohort were similar.

Conclusion

Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.

Objective

Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370.

Methods

Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers).

Results

We found no association with risk of ovarian cancer (OR=0.99, 95% CI 0.94-1.04, p=0.74) or breast cancer (OR=0.98, 95% CI 0.94-1.01, p=0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR=1.09, 95% CI 0.97-1.23, p=0.14, breast cancer HR=1.04, 95% CI 0.97-1.12, p=0.27; BRCA2, ovarian cancer HR=0.89, 95% CI 0.71-1.13, p=0.34, breast cancer HR=1.06, 95% CI 0.94-1.19, p=0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR=0.94, 95% CI 0.83-1.07, p=0.38), breast cancer (HR=0.96, 95% CI 0.87-1.06, p=0.38), and all other previously-reported associations.

Conclusions

rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.