Changing the Perspective on Fertility Preservation for Women with Metastatic or Advanced Stage Cancer.

PURPOSE OF REVIEW: In this Perspective we share the personal story of a 33-year-old patient diagnosed with metastatic breast cancer and her journey through fertility preservation, surrogacy, and eventually motherhood, highlighting misconceptions about fertility preservation in this population. RECENT FINDINGS: There are nearly 1 million women under the age of 50 diagnosed and living with cancer in the USA. These patients are met with life-altering decisions, including those that may limit their reproductive ability. While there have been tremendous advances and advocacy in the field of oncofertility, there has been limited focus on patients with advanced stage or metastatic cancer. We describe five key misconceptions surrounding fertility preservation in patients with advanced stage cancer, offering a review of the literature and our approach to challenging topics like desiring fertility preservation in the face of Stage 4 disease, the safety and timing of ovarian stimulation during cancer treatment, and passing away following fertility preservation. We review the importance of assessing perceptions of fertility preservation in patients with metastatic cancer and highlight the lack of research in this area as a call to action.

Successful treatment of stage IVB ovarian carcinosarcoma with PARP Inhibitor: A case report.

•Ovarian carcinosarcoma is a rare ovarian cancer histology that has limited treatment options.•In this study, we present an unusual association between carcinosarcoma and a STIC lesion.•In select patients with carcinosarcoma, PARP inhibition may provide clinical benefit.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database (NCDB).

PURPOSE: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer. METHODS: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses. RESULTS: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC who underwent lumpectomy had significantly higher positive margin rates (ILC 15.7% versus IDC 11.2%, p = 0.025). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden. CONCLUSION: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database.

Purpose: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer. Methods: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses. Results: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC had more positive margins (10.6% versus 8.3%, p = 0.005). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden. Conclusion: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

Cancer-directed surgery in patients with metastatic cancer: A systematic review and meta-analysis of randomized evidence.

PURPOSE: To assess the impact of primary-site surgery plus systemic therapy compared to systemic therapy alone on overall survival in common metastatic cancer types. METHODS: Data sources included Embase, PubMed, and Web of Science (January 1, 1995-March 22, 2023). Randomized controlled trials were included that enrolled patients diagnosed with the 10 most common de novo metastatic cancer types in the Surveillance, Epidemiology, and End Results database and randomized patients to resection of the primary site and systemic therapy versus systemic treatment alone. Random-effects models were used to pool associations by cancer type. RESULTS: Eight studies with 1774 patients evaluating the efficacy of surgery in breast, renal, stomach, and colorectal cancer were included. There was no statistically significant reduction in risk of all-cause mortality associated with surgical intervention for metastatic breast (HR = 0.94, 95% CI 0.63-1.40) or renal cancer (HR = 0.79, 95% CI 0.53-1.20), although results were heterogeneous (I2 = 73.7% and 80.6%, respectively). One study evaluating gastrectomy in metastatic stomach cancer found no benefit (HR = 1.09, 95% CI 0.78-1.52), while a small trial suggested that surgery and hyperthermic intraperitoneal chemotherapy might be beneficial for colorectal cancer with peritoneal metastasis (HR = 0.55, 95% CI 0.32-0.95). CONCLUSIONS: Few randomized trials have evaluated cancer-directed surgery among patients with metastatic solid malignancies.

Preparing for participation in the centers for Medicare and Medicaid Services' bundle care payment initiative-advanced for major bowel surgery.

BACKGROUND: As healthcare costs rise, there is an increasing emphasis on alternative payment models to improve care efficiency. The bundled payment represents an alternative reimbursement model gaining popularity within the surgical sphere. We aimed to assess where the largest opportunities for care improvement lay and how best to identify patients at high risk of suffering costly complications. METHODS: We utilized itemized CMS claims data for a retrospective cohort of patients between 2014 and 2016 who met inclusion criteria for the Major Bowel Bundled Payment Program and performed a cost analysis to identify opportunities for improved care efficiency. Based on the results of this cost analysis, we identified readmissions as a target for improvement. We then assessed whether the American College of Surgeons' National Surgical Quality Improvement Program surgical risk calculator (ACS NSQIP SRC) could accurately identify patients within our bundled payment population who were at high risk of readmission using a logistic regression model. RESULTS: Our study cohort included 252 patients. Readmissions accounted for 12.8% of the average total care episode cost with a coefficient of variation of 2.72, thereby representing the most substantial, non-fixed cost for our bundled payment patients. Patients readmitted within their 90-day care episode were 2.53 times more likely to be high-cost (>$60,000) than patients not readmitted. However, the ACS NSQIP SRC did not accurately predict patients at high risk of readmission within the first 30 days with an AUROC of 0.58. CONCLUSIONS: Our study highlights the importance of reducing readmissions as a central component of improving care for bowel surgery bundled payment patients. Preventing such readmissions requires accurate identification of patients at high risk of readmission; however, current risk prediction models lack the adaptability necessary for this task.

Hormone concentrations of dominant follicles in the TALES randomized controlled trial comparing letrozole with tamoxifen.

BACKGROUND: In this secondary analysis of the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) trial, we aimed to investigate if concurrent administration of letrozole vs. tamoxifen vs. no added treatment affects hormonal composition and size of stimulated ovarian follicles. METHODS: TALES is a randomized controlled trial of IVF stimulation for estrogen receptor (ER)-positive breast cancer patients stimulated with gonadotropins and administered concurrent tamoxifen 20 mg or letrozole 5 mg. We analyzed estradiol (E2), testosterone (T), progesterone (P4), follicle stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH). We used ANOVA/Kruskal-Wallis, logistic, and linear regression models to examine differences in follicular hormone levels, size, and mature oocyte yield between trial arm. RESULTS: We included data from total 246 follicles (94 letrozole, 82 tamoxifen, and 70 control) from 123 unique participants. E2 was lower (letrozole 187.4, tamoxifen 1026.0, control 821.5 ng/mL, p < 0.01) and T was higher (letrozole 2489, tamoxifen 571, and control 504 ng/mL, p < 0.03) in the letrozole group compared to tamoxifen and control groups, while other hormone levels and follicle size were similar across groups. There were no significant differences in hormone concentrations within the follicle between tamoxifen and control arms. On multivariate logistic regression, there was no significant association of mature oocyte yield by follicle size, hormone levels, or trial arm. CONCLUSIONS: Concurrent administration of letrozole with gonadotropins affects follicular E2 and T concentrations compared to tamoxifen/control. Tamoxifen was not associated with any differences in hormone concentrations within the follicle. Mature oocyte yield was similar across groups.

Molecular Imaging for Estrogen Receptor-Positive Breast Cancer: Clinical Applications of Whole Body and Dedicated Breast Positron Emission Tomography.

18F-fluoroestradiol (18F-FES) is a Food and Drug Administration-approved radiopharmaceutical used for molecular imaging of the estrogen receptor (ER). When combined with PET, 18F-FES may improve the diagnosis of ER-positive breast cancer in the metastatic setting and provide insights into tumor heterogeneity. In this article, we review data on the use of 18F-FES imaging for treatment selection, staging, imaging lobular breast cancer, and the novel breast specific imaging tool, dedicated breast PET.

Barriers to Colorectal Cancer Screening and Surveillance in Homeless Patients: A Case Report and Policy Recommendations.

Patients experiencing homelessness face significant barriers to screening and treatment for colorectal cancer, leading to worse outcomes. In this perspective, we use an exemplar patient case to highlight potential policy solutions for reducing this health care disparity by increasing access to early detection and treatment in this population.

Surgical Care of Patients Experiencing Homelessness: A Scoping Review Using a Phases of Care Conceptual Framework.

Homelessness is a growing concern across the world, particularly as individuals experiencing homelessness age and face an increasing burden of chronic health conditions. Although substantial research has focused on the medical and psychiatric care of patients experiencing homelessness, literature about the surgical care of these patients is sparse. Our objective was to review the literature to identify areas of concern unique to patients experiencing homelessness with surgical disease. A scoping review was conducted using a comprehensive database for studies from 1990 to September 1, 2020. Studies that included patients who were unhoused and discussed surgical care were included. The inclusion criteria were designed to identify evidence that directly affected surgical care, systems management, and policy making. Findings were organized within a Phases of Surgical Care framework: preoperative care, intraoperative care, postoperative care, and global use. Our search strategy yielded 553 unique studies, of which 23 met inclusion criteria. Most studies were performed at public and/or safety-net hospitals or via administrative datasets, and surgical specialties that were represented included orthopedic, cardiac, plastic surgery trauma, and vascular surgery. Using the Surgical Phases of Care framework, we identified studies that described the impact of housing status in pre- and postoperative phases as well as global use. There was limited identification of barriers to surgical and anesthetic best practices in the intraoperative phase. More than half of studies (52.2%) lacked a clear definition of homelessness. Thus, there is a marked gap in the surgical literature regarding the impact of housing status on optimal surgical care, with the largest area for improvement in the intraoperative phase of surgical and anesthetic decision making. Consistent use of clear definitions of homelessness is lacking. To promote improved care, a standardized approach to recording housing status is needed, and studies must explore vulnerabilities in surgical care unique to this population.

The 21-Gene Recurrence Score in Clinically High-Risk Lobular and Ductal Breast Cancer: A National Cancer Database Study.

OBJECTIVE: The aim of this study was to evaluate whether patients with invasive lobular carcinoma (ILC) are more likely to have discordant clinical and genomic risk than those with invasive ductal carcinoma (IDC) when using the 21-gene recurrence score (RS), and to assess overall survival outcomes of patients with 1-3 positive nodes and RS ≤25 with and without chemotherapy, stratified by histology. METHODS: We performed a cohort study using the National Cancer Database and included patients with hormone receptor-positive, HER2-negative, stage I-III invasive breast cancer who underwent 21-gene RS testing. Our primary outcome was rate of discordant clinical and genomic risk status by histologic subtype. Propensity score matching was used to compare 60-month overall survival in individuals with 1-3 positive nodes and RS ≤25 who did and did not receive chemotherapy. RESULTS: Overall, 186,867 patients were included in our analysis, including 37,685 (20.2%) patients with ILC. There was a significantly higher rate of discordant clinical and genomic risk in patients with ILC compared with IDC. Among patients with 1-3 positive nodes and RS ≤25, there was no significant difference in survival between those who did and did not receive chemotherapy in the IDC or ILC cohorts. Unadjusted exploratory analyses of patients under age 50 years with 1-3 positive nodes and RS ≤25 showed improved overall survival in IDC patients who received chemotherapy, but not among those with ILC. CONCLUSION: Our findings highlight the importance of lobular-specific tools for stratifying clinical and genomic risk, as well as the need for histologic subtype-specific analyses in randomized trials.

Impact of COVID-19 on the Incidence and Severity of Obstetric and Gynecologic Emergency Department Visits in an Integrated Health Care System.

OBJECTIVE: COVID-19 has had an unprecedented impact on medical care use and delivery, including stark reductions in emergency department (ED) volume. The aim of this study was to assess changes in incidence of OB/GYN ED visits and disease severity at time of presentation during the COVID-19 pandemic. STUDY DESIGN: We conducted a multicenter retrospective study of OB/GYN-related ED visits before and during the COVID-19 pandemic. Incidence rates (IRs) and severity measures were compared across time periods and years. RESULTS: A total of 18,668 OB/GYN ED encounters occurred between January 1 and December 31, 2020, compared to 21,014 encounters between January 1 and December 31, 2019. During shelter-in-place, visits decreased by 41% compared to the pre-pandemic period in 2020 before returning to typical rates (incidence rate ratio (IRR) = 0.98 in fall/winter). We found a similar proportion of patients with hemoglobin < 7 g/dL for diagnoses associated with bleeding and patients with white blood cell count > 12,000 per µL in the setting of infection comparing corresponding time periods in 2019 and 2020. There were fewer formal OB/GYN consults, hospital admissions at time of presentation, and urgent surgical procedures performed across all periods in 2020; however, hospitalization within 7 days substantially increased in the first half of 2020. CONCLUSION: The incidence of OB/GYN ED visits declined substantially between March and August 2020 but then returned to pre-pandemic levels by fall/winter 2020. The decreased incidence was not accompanied by an increase in severity of presentation.

Gynecological management of the breast cancer survivor.

Survival from breast cancer has continued to increase since the 1990's, and quality of life and gynecologic issues have been an increasingly important part of overall care. Common women's health issues such as contraception, pregnancy, menopause, and sexual functioning are uniquely affected by breast cancer diagnosis and treatment. Two-thirds of breast cancers are hormone-sensitive and adjuvant hormonal therapies like tamoxifen or aromatase inhibitors have substantially decreased the disease recurrence and contralateral breast cancer. These hormonal therapies can cause menopausal and sexual side effects, and women's healthcare providers need to understand safe and effective treatment options to manage them. Providing counseling and evidence-based education is important for primary care providers and gynecologists who care for those women who have or previously had breast cancer. This review will focus on specific women's health issues pertaining to breast cancer and treatment.

Breast cancer grade and stage do not affect fertility preservation outcomes.

PURPOSE: To investigate if breast cancer stage and grade affect fertility preservation outcomes. METHODS: We performed a retrospective cohort study that included premenopausal women with breast cancer undergoing fertility preservation diagnosed between January 2011 and January 2019. The primary outcome measure was the number of mature oocytes (MII) per antral follicle count (AFC). Secondary outcome measures included total oocytes retrieved, total mature oocytes retrieved, and greater than 10 mature oocytes preserved. Univariate and multivariate models were used to assess the association of low vs. high stage (low stage I-II and high stage III-IV) and grade I vs. grade II/III with each outcome, with adjustment for confounders. RESULTS: A total of 267 premenopausal breast cancer patients undergoing fertility preservation were included in our study, with the majority presenting with low stage (N = 215, 80.5%), grade II/III (N = 235, 88.1%) disease. Baseline AFC, total gonadotropin dose, days of stimulation, and follicles [Formula: see text] 13 mm on the day of trigger did not differ by stage or grade. After adjusting for age, BMI, and baseline AFC, we found that the mean MII per AFC did not differ by stage (1.0 vs. 1.1, P = 0.3) or grade (1.0 vs. 1.0, P = 0.92). Similarly, total oocytes retrieved, total MII retrieved, and percentage of patients who were able to preserve greater than 10 MII did not differ by breast cancer stage or grade (all P > 0.2). CONCLUSION: Breast cancer grade and stage do not impact ovarian stimulation or fertility preservation outcome.

Obesity and menopausal status impact the features and molecular phenotype of invasive lobular breast cancer.

PURPOSE: We investigated the relationship between obesity, menopausal status, and invasive lobular carcinoma (ILC), the second most common histological subtype of breast cancer. Specifically, we evaluated the association between body mass index (BMI), metabolic syndrome, the 21-gene Oncotype Recurrence Score (Oncotype RS), and pathological features in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor-2-negative ILC. METHODS: The study cohort included 491 patients from a prospectively maintained institutional database consisting of patients with stage I-III, HR-positive ILC who underwent surgical treatment between 1996 and 2019. RESULTS: Contrary to our expectations, we found that lower BMI was significantly associated with having higher Oncotype RS (18.9% versus 4.8%, p = 0.028) in post-menopausal patients, but was not related to tumor characteristics in pre-menopausal patients. Multivariate network analyses suggested a strong relationship between post-menopausal status itself and tumor characteristics, with lesser influence of BMI. CONCLUSION: These findings provide further insight into the recently appreciated heterogeneity within ILC and support the need for further investigation into the drivers of this disease and tailored treatment strategies.

The incidence of discordant clinical and genomic risk in patients with invasive lobular or ductal carcinoma of the breast: a National Cancer Database Study.

When molecular testing classifies breast tumors as low risk but clinical risk is high, the optimal management strategy is unknown. One group of patients who may be more likely to have such discordant risk are those with invasive lobular carcinoma of the breast. We sought to examine whether patients with invasive lobular carcinoma are more likely to have clinical high/genomic low-risk tumors compared to those with invasive ductal carcinoma, and to evaluate the impact on receipt of chemotherapy and overall survival. We conducted a cohort study using the National Cancer Database from 2010-2016. Patients with hormone receptor positive, HER2 negative, stage I-III breast cancer who underwent 70-gene signature testing were included. We evaluated the proportion of patients with discordant clinical and genomic risk by histology using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models with and without propensity score matching. A total of 7399 patients (1497 with invasive lobular carcinoma [20.2%]) were identified. Patients with invasive lobular carcinoma were significantly more likely to fall into a discordant risk category compared to those with invasive ductal carcinoma (46.8% versus 37.1%, p < 0.001), especially in the clinical high/genomic low risk subgroup (35.6% versus 19.2%, p < 0.001). In unadjusted analysis of the clinical high/genomic low-risk cohort who received chemotherapy, invasive ductal carcinoma patients had significantly improved overall survival compared to those with invasive lobular carcinoma (p = 0.02). These findings suggest that current tools for stratifying clinical and genomic risk could be improved for those with invasive lobular carcinoma to better tailor treatment selection.