Fulfilling the Role of a Parent While Undergoing Treatment for Cancer: A Review of the Literature and the Potential Impact of Childcare Support on Cancer Outcomes.

Breast cancer is the most prevalent malignancy among adolescents and young adults (AYAs). Despite the efficacy of chemotherapy, AYA patients contend with psychosocial challenges, including psychological distress and financial toxicity, exacerbated further by those with dependent children. Parenting responsibilities intersect with cancer care, impacting both family dynamics and treatment adherence. Despite recognized needs, however, the impact of parenting concerns or even parenting status and the presence of dependents has not been systematically addressed and there is a paucity of interventional research regarding patients with cancer as concomitant caregivers. A feasibility study conducted by the Brown University Oncology Cooperative Group demonstrated the potential benefits of providing financial assistance for childcare, both improving treatment adherence and reducing distress among participants. Similar interventions have shown promise in addressing financial hardships for AYA patients with cancer who are concomitant caregivers. Ultimately, parenting concerns have a significant impact on medical decision-making, and further interventional research on childcare support is required to examine the ways in which health systems can improve family stability, stress, and quality of life.

Treatment-induced sarcoidosis in a patient with metastatic clear cell ovarian cancer.

Sarcoidosis is a granulomatous disease that commonly presents with lung or lymphatic system manifestations. Diagnosis is often delayed due to variable clinical presentation. This is a case of a patient with metastatic clear cell ovarian cancer who developed disease reoccurence after definitive treatment with surgery and adjuvant chemotherapy. She was treated with multiple lines of therapy, including investigational agents. During this time, she developed mediastinal lymphadenopathy and hypercalcaemia. Due to suspicion that her presentation was not a manifestation of her malignancy, she underwent two lymph node biopsies revealing granulomatous disease. She was initiated on prednisone for management of sarcoidosis, which led to radiologic, laboratory and symptomatic improvement. Although the precipitating factor for this patient's sarcoidosis cannot be definitively determined, nivolumab is a possible culprit. This case highlights the importance of a broad differential diagnosis when a patient undergoing antineoplastic treatment develops mediastinal lymphadenopathy or hypercalcaemia.

How Does Invasive Breast Cancer Oncotype Dx Recurrence Score on Core Needle Biopsies Influence Neoadjuvant Treatment Decision? A Descriptive Study.

BACKGROUND: Oncotype Dx (ODx) is a genomic assay which estimates the risk of distant recurrence and predicts adjuvant chemotherapy benefit in early stage breast cancer patients. Most ODx data is derived from excisional specimens. AIM: We assess the utility of ODx on core needle biopsies (CNB) and measure its impact on neoadjuvant treatment decisions, particularly in patients with clinically complicated situations. METHODS: Consecutive ODx results on breast CNBs with invasive carcinoma from 2012-2020 at 3 tertiary care hospitals with dedicated Breast Health Centers were reviewed. Clinical indications to perform ODx on CNB were recorded through a review of patients' electronic medical records. Clinicopathologic features, surgical or oncologic modalities and follow-up data were recorded. RESULTS: Three distinct clinical indications for performing ODx on CNB in 85 ER+ invasive breast carcinomas were identified: 1) Excisions with insufficient tissue to perform ODx, 2) adjudicate neoadjuvant therapy versus primary surgical resection, and 3) select neoadjuvant chemotherapy (NAC) versus neoadjuvant endocrine therapy (NET). Primary surgery was selected in patients with low score RS (<18), and NET was preferred in patients with intermediate or high RS (>18). NET was preferred over NAC in patients with low RS (<18). CONCLUSION: This study shows that CNB ODx RS helps guide treatment decisions in a neoadjuvant setting along with other contributing factors such as the presence of pathogenic mutations, node positivity, patient age, and comorbidities. The use of ODx on CNB is furthermore valuable in the midst of the COVID-19 pandemic for early breast cancer patients to administer effective therapy in a timely manner.

Pertuzumab-associated diarrhea in HER2/neu-positive breast cancer patients: A comparison of trials to actual practice.

BACKGROUND: Although landmark trials in the metastatic (CLEOPATRA) and neo-adjuvant (NeoSphere; TRYPHAENA) settings identified all-grade diarrhea as a pertuzumab-associated adverse event, it was not classified as dose-limiting. In actual practice, diarrhea is often a reason for treatment modifications. OBJECTIVES: To compare the risk of pertuzumab-associated diarrhea in actual practice to the risks in randomized controlled trials. METHODS: We conducted a retrospective cohort study of HER2/neu-positive breast cancer patients who received a pertuzumab-containing regimen between January 2012 and August 2015. We calculated the risk of diarrhea with 95% confidence limits (CLs), and then used two-sample t-tests to compare the risk between trials and actual practice. RESULTS: A total of 27 patients in the study cohort received a pertuzumab-containing treatment regimen for HER2/neu-positive breast cancer. The overall risk of all-grade and severe diarrhea in actual practice was 70% (95% CLs 55-90%) and 37% (95% CLs 20-66%), respectively. No severe diarrhea was observed in the metastatic setting, and the risk of all-grade diarrhea (44%, 95% CLs 21-92%) was similar to the CLEOPATRA study (67%). The risk of all-grade diarrhea in the neo-adjuvant setting was 83% (95% CLs 68-100%), compared to 46% in the NeoSphere trial (p = 0.03). The risk of severe diarrhea (Grade 3-4) in the neo-adjuvant setting was 47% (95% CLs 27-80%) versus 6% in the NeoSphere (p < 0.0001) and 12% in the TRYPHAENA (p < 0.01) trials. CONCLUSIONS: The risk of all-grade and severe diarrhea associated with neoadjuvant pertuzumab use for HER2/neu-positive breast cancer was greater in actual practice than in trials.

Distress: Characterizing What Causes the Thermometer to Shift in Patients with Newly Diagnosed Breast Cancer Attending a Multidisciplinary Clinic.

BACKGROUND: A diagnosis of breast cancer (BC) can result in multifactorial stress. If not addressed, distress can have a negative impact on outcomes. The experience of patients with newly diagnosed BC has not been sufficiently investigated. This study characterizes distress among new patients in a multidisciplinary care (MDC) clinic. The study aimed to determine the degree of distress at presentation, to characterize the sources, and to evaluate the impact of an MDC visit. METHODS: A retrospective review was performed from January 2015 to November 2017. Charts were accessed for demographics, tumor characteristics, and treatment data. Distress scores (DS) and problems as captured using the National Comprehensive Cancer Network (NCCN) Distress Thermometer were completed before evaluation and in a subgroup after an MDC visit. Predictors of severe distress (DS ≥4) were investigated using multivariable logistic regression. The paired t test was used to determine the impact of an MDC visit. RESULTS: The mean initial DS (n = 474) was 4.98. The top four sources of distress were worry, anxiety, fears, and sadness. Age younger than 65 years was significantly associated with a higher DS at presentation (p < 0.003). Among the patients queried before and after MDC (n = 137), a significant reduction in distress was identified (5.58-2.94; p < 0.0005). CONCLUSIONS: Severe distress was found in 66 % of the patients with a recent diagnosis of BC, with younger age related to higher distress scores at presentation. Emotional stressors were the predominant factors accounting for distress. A same-day MDC visit was associated with a significant reduction in DS. These data indicate the importance and feasibility of proactively screening patients. Our research lends support to the value of multidisciplinary evaluation in this setting.

New Approaches to Improving Survival After Neoadjuvant Chemotherapy: The Role of Intraperitoneal Therapy and Heated Intraperitoneal Chemotherapy in Ovarian Cancer.

For women with newly diagnosed ovarian cancer, the goal of surgery is to achieve a maximal, if not complete, cytoreduction. In cases when this is not possible, whether because of the extent of disease or patient-specific reasons, neoadjuvant chemotherapy using a platinum-based combination (on a typical every-2-week schedule) is often recommended. After neoadjuvant therapy and surgery, women proceed with additional adjuvant chemotherapy, which is typically given in a similar fashion to what was done in the preoperative setting. The question remains as to whether this is the optimal strategy, particularly in light of other data suggesting the use of an alternative regimen in the adjuvant context might yield a survival advantage. In this article, we review the outcomes of randomized trials that compared primary debulking to neoadjuvant chemotherapy and contemporary neoadjuvant chemotherapy trials that incorporated a novel schedule or regimen for testing in the adjuvant setting, including both intraperitoneal and heated intraperitoneal chemotherapy. We describe our center's approach to these data, and we conclude that both options should be considered for women with ovarian cancer undergoing neoadjuvant therapy.

Sexuality, fertility and pregnancy following breast cancer treatment.

For women facing a new diagnosis of breast cancer, treatments can result in changes to intimate issues, including sexual health. For women of reproductive age, other significant concerns include the potential impact on fertility and the safety of pregnancy after treatment. These issues are important to acknowledge and to address, as they can impact on quality of life, not only for the patient, but may impact relationships, both present and future. In this paper we review sexual health after cancer, the importance of proactively addressing fertility, and important issues related to pregnancy following breast cancer.

Stromal Clusterin Expression Predicts Therapeutic Response to Neoadjuvant Chemotherapy in Triple Negative Breast Cancer.

BACKGROUND: Expression of clusterin correlates with tumor progression and therapeutic response in several human malignancies, including breast cancer. However, its predictive value in the neoadjuvant setting in breast cancer remains unexplored. The objective of this explorative study was to determine whether clusterin expression in breast cancer correlated with clinical pathologic characteristics and whether its expression was predictive of response to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: We determined the clusterin expression pattern in 72 triple negative breast cancers (TNBC) treated with NAC before surgery. Clusterin expression was evaluated by immunohistochemistry and was correlated with pathologic characteristics and response to NAC using residual cancer burden score. RESULTS: Immunohistochemistry analysis revealed a differential pattern of expression between tumor and stroma. Clusterin expression in the tumor associated stroma as opposed to expression by the neoplastic epithelium was significantly associated with neoadjuvant-treated TNBC. Low stromal clusterin, low stromal content, and high tumor-infiltrating lymphocytes were associated with a significantly greater likelihood of achieving a good pathologic response as reflected by lower residual cancer burden scores (P = .002, P = .003, and P = .001, respectively). Tumor and/or stromal clusterin expression were not associated with patient age, tumor histologic grade, stage, and lymph node status. CONCULSION: This study suggests a potential role for the assessment of stromal clusterin as a predictive biomarker for response of TNBC to neoadjuvant therapy. Further validation of this biomarker in a large study is needed.

Prenatal Maternal Physical Activity and Stem Cells in Umbilical Cord Blood.

PURPOSE: Early life processes, through influence on fetal stem cells, affect postnatal and adult health outcomes. This study examines the effects of physical activity before and during pregnancy on stem cell counts in umbilical cord blood. METHODS: We isolated mononuclear cells from umbilical cord blood samples from 373 singleton full-term pregnancies and quantified hematopoietic (CD34(+), CD34(+)CD38(-), and CD34(+) c-kit(+)), endothelial (CD34(+)CD133(+), CD34(+)CD133(+)VEGFR2(+), CD34(+)VEGFR2(+), and CD133(+)VEGFR2(+)), and putative breast (EpCAM(+), EpCAM(+)CD49f(+), EpCAM(+)CD49f(+)CD117(+), CD49f(+)CD24(+), CD24(+)CD29(+), and CD24(+)CD29(+)CD49f(+)) stem/progenitor cell subpopulations by flow cytometry. Information on physical activities before and during pregnancy was obtained from questionnaires. Weekly energy expenditure was estimated based on metabolic equivalent task values. RESULTS: Prepregnancy vigorous exercise was associated positively with levels of endothelial CD34(+)CD133(+), CD34(+)CD133(+)VEGFR2(+), CD34(+)VEGFR2(+), and CD133(+)VEGFR2(+ )progenitor cell populations (P = 0.02, P = 0.01, P = 0.001, and P = 0.003, respectively); positive associations were observed in samples from the first births and those from the second or later births. Prepregnancy moderate and light exercises and light exercise during the first trimester were not significantly associated with any stem/progenitor cell population. Light exercise during the second trimester was positively associated with CD34(+)VEGFR2(+) endothelial progenitor cells (P = 0.03). In addition, levels of EpCAM(+)CD49f(+) and CD49f(+)CD24(+) breast stem cells were significantly lower among pregnant women who engaged in vigorous/moderate exercise during pregnancy (P = 0.05 and P = 0.02, respectively). CONCLUSIONS: Vigorous exercise before pregnancy increases the number of endothelial progenitor cells in umbilical cord blood and thus could potentially enhance endothelial function and improve cardiovascular fitness in the offspring. Findings of lower levels of putative breast stem cell subpopulations could have implications on exercise and breast cancer prevention. Prenatal effects of exercise on fetal stem cells warrant further studies.

Effect of preeclampsia on umbilical cord blood stem cells in relation to breast cancer susceptibility in the offspring.

Women born from a preeclamptic (PE) pregnancy are associated with a lower risk of breast cancer. Prenatal and early-life exposures are hypothesized to influence breast cancer susceptibility through their effect on stem cells. We examined stem cell populations in umbilical cord blood from PE pregnancies and compared with those from pregnancies without this condition. We isolated mononuclear cells from 58 PE and 197 normotensive (non-PE) umbilical cord blood samples and examined the different stem cell populations. Hematopoietic (CD34(+) and CD34(+)CD38(-)), endothelial (CD34(+)CD133(+), CD34(+)VEGFR2(+), CD133(+)VEGFR2(+) and CD34(+)CD133(+)VEGFR2(+)), and putative breast (EpCAM(+), EpCAM(+)CD49f(+), EpCAM(+)CD49f(+)CD117(+), CD49f(+)CD24(+), CD24(+)CD29(+) and CD24(+)CD29(+)CD49f(+)) stem/progenitor cell subpopulations were quantified by flow cytometry and compared between PE and non-PE samples. Hematopoietic CD34(+) cell counts were significantly lowered in PE compared with non-PE samples (P = 0.039, Kruskal-Wallis test). Levels of CD34(+)CD133(+) endothelial progenitor cells were also lower in PE samples (P = 0.032, multiple regression analysis). EpCAM(+) and EpCAM(+)CD49f(+) putative breast stem cell levels were significantly lowered in PE subjects (multiple regression analysis: P = 0.038 and 0.007, respectively). Stratifying by newborn gender, EpCAM(+) and EpCAM(+)CD49f(+) stem cells were significantly lowered in PE samples of female, but not male, newborns. Umbilical cord blood samples from pregnancies complicated by preeclampsia thus had significantly lower levels of hematopoietic, endothelial, and putative breast stem cells than non-PE controls. With a lowered breast cancer risk for offspring of a PE pregnancy, our findings provide support to the hypothesis that susceptibility to breast oncogenesis may be affected by conditions and processes during the prenatal period.