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.

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.

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.

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.