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Background: Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. Methods: Patients with stage I–III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. Results: Of 126 patients approached, 56 (44%) enrolled. Forty‐five (80%) received ≥1 dose of memantine and completed pre‐post assessments. Seventy‐six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty‐four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%–91% across objective cognitive domain composite measures. Sixty‐six percent self‐reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. Conclusions: Memantine was well‐tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre‐ to post‐assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. Trial Registration: ClinicalTrials.gov NCT04033419. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, it is unknown whether patient‐reported symptom severity and symptom interference with daily activities differ between younger (aged <65 years) and older (aged ≥65 years) women receiving similar chemotherapy regimens for early breast cancer (EBC). Methods: Study participants rated 17 side effects of chemotherapy regimens currently in use in clinical practice (2014‐2019). Results: Of 284 women with EBC (stage I‐III), approximately 57% were aged <65 years and 43% were aged ≥65 years. For anthracycline‐based regimens, a higher percentage of younger women reported moderate, severe, or very severe (MSVS) hot flashes (49% vs 18%) (P <.001). For nonanthracycline regimens, a higher percentage of younger women reported MSVS hot flashes (38% vs 19%) (P =.009) and a lower percentage reported MSVS arthralgia (28% vs 49%) (P =.005). With regard to symptom interference with daily activities, a higher percentage of younger women being treated with anthracycline‐based regimens reported MSVS hot flashes (32% vs 7%) (P =.001) and myalgia (38% vs 18%) (P =.02). For nonanthracycline chemotherapy, a higher percentage of younger women reported MSVS interference for hot flashes (26% vs 9%) (P =.006) and lower percentages reported abdominal pain (13% vs 28%) (P =.02). Overall, there were no significant differences noted among younger versus older patients with regard to hospitalizations (19% vs 12%; P =.19), dose reductions (34% vs 31%; P =.50), dose delays (22% vs 25%; P =.59), or early treatment discontinuation (16% vs 16%; P =.9546). Conclusions: Older and younger women with EBC who were treated with identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom‐related interference with daily activities, and adverse events. Lay Summary: In this study, women receiving chemotherapy for early breast cancer rated the severity of 17 symptoms and symptom interference with their activities of daily living.Older (aged ≥65 years) and younger (aged <65 years) women who received identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom‐related interference with daily activities, and adverse events. In the current study, women receiving chemotherapy for early breast cancer rate the severity of 17 symptoms and symptom interference with their activities of daily living. Older (aged ≥65 years) and younger (aged <65 years) women who received identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom‐related interference with daily activities, and adverse events. [ABSTRACT FROM AUTHOR]

Background Although chemotherapy saves lives, increasing evidence shows that chemotherapy accelerates aging. We previously demonstrated that mRNA expression of p16INK4a , a biomarker of senescence and molecular aging, increased early and dramatically after beginning adjuvant anthracycline-based regimens in early stage breast cancer patients. Here, we determined if changes in p16INK4a expression vary by chemotherapy regimen among early stage breast cancer patients. Methods We conducted a study of stage I-III breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. p16INK4a expression was analyzed prechemotherapy and postchemotherapy (median 6.2 months after the last chemotherapy) in peripheral blood T lymphocytes. Chemotherapy-induced change in p16INK4a expression was compared among regimens. All statistical tests were 2-sided. Results In 146 women, chemotherapy was associated with a statistically significant increase in p16INK4a expression (accelerated aging of 17 years; P <.001). Anthracycline-based regimens were associated with the largest increases (accelerated aging of 23 to 26 years; P ≤.008). Nonanthracycline-based regimens demonstrated a much smaller increase (accelerated aging of 9 to 11 years; P ≤.15). In addition to the type of chemotherapy regimen, baseline p16INK4a levels, but not chronologic age or race, were also associated with the magnitude of increases in p16INK4a. Patients with lower p16INK4a levels at baseline were more likely to experience larger increases. Conclusions Our findings suggest that the aging effects of chemotherapy may be influenced by both chemotherapy type and the patient's baseline p16INK4a level. Measurement of p16INK4a expression is not currently available in the clinic, but nonanthracycline regimens offering similar efficacy as anthracycline regimens might be favored. [ABSTRACT FROM AUTHOR]

Background. Breast cancer brain metastasis (BCBM) confers a poor prognosis and is unusual in requiring multidisciplinary care in the metastatic setting. The University of North Carolina at Chapel Hill (UNC-CH) has created a BCBM clinic to provide medical and radiation oncology, neurosurgical, and supportive services to this complex patient population. We describe organization and design of the clinic as well as characteristics, treatments, and outcomes of the patients seen in its first 3 years. Methods. Clinical and demographic data were collected from patients in a prospectively maintained database. Descriptive statistics are reported as percentages and means. The Kaplan-Meier method was used to estimate time-to-event outcomes. Results. Sixty-five patients were seen between January 2012 and January 2015. At the time of presentation to the BCBM clinic, most patients (74%) had multiple (≥2) brain metastases and had received prior systemic (77%) and whole-brain radiation therapy and/or central nervous system stereotactic radiosurgery (65%) in the metastatic setting. Seventy-eight percent returned for a follow-up visit; 32% were enrolled in a clinical trial. Median time from diagnosis of brain metastasis to death was 2.11 years (95% confidence interval [CI] 1.31-2.47) for all patients, 1.15 years (95% CI 0.4-2.43) for triple-negative breast cancer, 1.31 years (95% CI 0.51-2.52) for hormone receptor-positive/HER22 breast cancer, and 3.03 years (95% CI lower limit 1.94, upper limit not estimable) for HER21 breast cancer (p = .0037). Conclusion. Patients with BCBM have unique and complex needs that require input from several oncologic disciplines. The development of the UNC-CH multidisciplinary BCBM clinic is a model that can be adapted at other centers to provide coordinated care for patients with a challenging and complex disease. [ABSTRACT FROM AUTHOR]

Objective: We sought to explore whether post-traumatic growth (PTG) (positive change or benefit finding resulting from trauma) moderates relationships between post-traumatic stress symptoms (PTSS) and both depression and quality of life (QOL) among breast cancer survivors. Methods: We interviewed 161 women previously treated for early stage breast cancer. We assessed PTG using the Post-traumatic Growth Inventory, PTSS using the PTSD Checklist, depressive symptoms using the CES-D and QOL using the FACT-B. Results: Higher PTSS was associated with greater depressive symptoms and lower QOL (p<0.01). The relationship between PTSS and depression was attenuated among women with higher levels of PTG (PTSS × PTG interaction, p<0.05). The same pattern of results was found for QOL (interaction p<0.01). Conclusions: We report the novel finding that PTG moderated relationships between PTSS and both depression and QOL. We speculate that finding positive meaning in response to a distressing event, such as diagnosis of cancer, may be psychologically protective and could indirectly influence the long-term occurrence of depressive symptoms and impaired QOL. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Ductal carcinoma in situ (DCIS) has a generally favorable overall prognosis, with a systemic recurrence rate of approximately 1%, a local recurrence rate after mastectomy of 1%, and a local recurrence rate after breast-conserving treatment of less than 10%. Preliminary studies have suggested that women with DCIS may overestimate their risk of disease recurrence. Few data exist regarding psychosocial outcomes for women with DCIS. Methods Women in Eastern Massachusetts with newly diagnosed DCIS were asked to participate in a longitudinal study of risk perceptions, psychosocial concerns, and health behaviors. Psychosocial outcomes after DCIS diagnosis and risk perceptions were evaluated at enrollment and at 9 and 18 months. All statistical tests were two-sided. Results Four hundred eighty-seven women with DCIS (64% of eligible participants) completed the enrollment survey. Overall quality of life was good among the women surveyed, and the substantial anxiety at enrollment decreased with time (P < .001). At enrollment, 54% perceived at least a moderate risk for DCIS recurrence in the next 5 years, 68% in their lifetime; 39% perceived at least a moderate risk for invasive cancer in the next 5 years, 53% in their lifetime; and 28% perceived at least a moderate likelihood of DCIS spreading to other places in their body. At 18 months after enrollment, perceived risks had not statistically significantly changed from those at enrollment (P = .38). Anxiety at enrollment was the factor that was most consistently and strongly associated with overestimation of future breast cancer-related risks (perceived moderate or greater risk vs less than moderate risk of DCIS recurring within 5 years: odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.6 to 9.9, P= .003; of invasive breast cancer within 5 years: OR = 4.3, 95% CI = 1.9 to 9.9, P < .001; and of invasive breast cancer during lifetime: OR = 5.3, 95% CI = 2.0 to 14.3, P < .001). Conclusions Many women with newly diagnosed DCIS have inaccurate perceptions of the breast cancer risks that they face, and anxiety is particularly associated with these inaccurate perceptions. [ABSTRACT FROM AUTHOR]

Breast cancers diagnosed during pregnancy and lactation typically have an aggressive phenotype and an advanced stage at presentation. The timing of treatment modalities in pregnant women is complex and requires multidisciplinary input. Alternatives which are relatively safe for both mother and fetus are available, though unforeseen risks may exist. Chemotherapy is not thought to be safe for a fetus during the first trimester; however, in women with high risk cancers, treatment should not be delayed. Thereafter, anthracycline based chemotherapy has a low incidence of fetal complications. Little evidence beyond case reports exists for taxanes or tamoxifen in pregnancy, and less is available regarding the safety of novel molecularly targeted therapeutics such as trastuzumab. The prognosis of breast cancer diagnosed during pregnancy and lactation is poor, largely because of advanced stage and aggressive phenotype; it is unclear whether pregnancy is an independent prognostic marker for poor outcome. [ABSTRACT FROM AUTHOR]

Background: Response to neoadjuvant chemotherapy is used as an intermediate endpoint for breast cancer relapse and survival. Most breast cancer response classification systems use pathologic complete response, either alone or in conjunction with clinical assessments, to categorize response. We examined the ability of the revised 2003 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, which considers both the number of involved axillary lymph nodes and the extent of tumor in the breast to predict patient survival after neoadjuvant chemotherapy for breast cancer.Methods: We assessed the pathologic stage of residual tumor in 132 patients with nonmetastatic breast cancer after they had undergone neoadjuvant chemotherapy and examined the association between AJCC TNM stage and subsequent distant disease-free survival and overall survival. All statistical tests were two-sided.Results: At a median follow-up of 5 years, pathologic stage in the surgical specimens after neoadjuvant chemotherapy using the revised AJCC system was strongly associated with both distant disease-free survival and overall survival. A higher pathologic stage of residual tumor after neoadjuvant chemotherapy was associated with a statistically significant lower rate of distant disease-free survival (stage 0: 95%, stage I: 84%, stage II: 72%, and stage III: 47%; Ptrend < .001). The 5-year distant disease-free survival for patients with residual stage IIIC tumors was only 18% (95% CI = 0% to 36%).Conclusion: Classification of residual tumor in the breast and axillary surgical specimens after neoadjuvant chemotherapy using the revised AJCC TNM system is useful for predicting distant relapse and survival. [ABSTRACT FROM AUTHOR]

Purpose. Immunotherapy using either dendritic cells (DCs) or expanded cytotoxic T cells (CTLs) has received increased interest in the treatment of specific malignancies including metastatic breast cancer (MBC). DCs can be generated ex vivo from monocytes or CD34+ precursors. The ability to expand and safely administer CD34-derived DCs in patients with MBC that have received prior cytotoxic chemotherapy has not been evaluated. Methods. We enrolled ten patients with MBC that had received prior chemotherapy for the treatment of metastatic disease on a phase I/II trial designed to test the safety and feasibility of administering ex vivo expanded DCs from CD34+ progenitor cells. Results. Using a cocktail of multiple different cytokines, we could expand DCs 19-fold compared to the initial CD34-selected product, which allowed the administration of as many as six vaccine treatments per patient. Patients received three to six injections i.v. of DCs pulsed with either the wild type GP2 epitope from the HER-2/neu protein or an altered peptide ligand, isoleucine to leucine (I2L). Toxicity was mild, with no patients demonstrating grade III toxicity during the treatment. Two patients with subcutaneous disease had a partial response to therapy, while IFN-γ-producing CD8+ T cells could be found in two other patients during treatment. Conclusions. This approach is safe and effective in generating a significant quantity of DCs from CD34-precursors. [ABSTRACT FROM AUTHOR]

Background: Retrieval of fewer than 10 lymph nodes at axillary dissection (ALND) for breast cancer can represent anatomic variation or inadequate dissection. We postulated that despite aggressive ALND, a lower lymph node count is more frequent after neoadjuvant chemotherapy.Methods: Patients who received neoadjuvant chemotherapy followed by ALND were compared with patients who received surgery first. All patients received a level I and II ALND at a single institution by one of the breast surgeons. The number of nodes retrieved at ALND was dichotomized into categories (< 10 and > or = 10), and compared using Fisher exact test.Results: A total of 143 neoadjuvant and 170 surgery-first patients were studied. Patients treated with neoadjuvant chemotherapy were significantly more likely to have fewer than 10 lymph nodes retrieved at ALND than were the surgery-first patients (19/143 or 13% vs. 6/170 or 4%, P = .003).Conclusions: A low lymph node count is more common in patients after treatment with neoadjuvant chemotherapy and should not be assumed to represent an incomplete ALND. [ABSTRACT FROM AUTHOR]