Search

The article presents abstracts on medical topics which include acute chemotherapy-related toxicity in BRCA1 and BRCA2 mutation carriers treated for breast cancer in Great Britain, neoadjuvant endocrine therapy for locally advanced breast cancer, and human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer.

Background: CTX induced hair loss (HL) is one of the most distressing side effects of BC treatment. Compared to women without CTX induced alopecia, those with alopecia have reported poorer body image, lower self-esteem and worse quality of life. In some cases, CTX induced HL may affect choice of therapy. Given the emotional impact of HL, the potential benefit of preventing CTX induced alopecia is great. We conducted a registry study tracking safety and efficacy in BC patients (pts) treated at our center who independently elected to use Penguin Cold Cap Therapy (PCCT). Methods: Pts who chose to use PCCT during CTX for early stage (ES) or advanced (M) disease signed informed consent to participate in the registry. HL was rated by practitioner assessment using the 5 point Dean's scale for HL: grade 0 (no HL), 1 (< 25% HL), 2 (25-50% HL), 3 (50-75% HL), and 4 (>75% HL), and by pt assessment using a visual analogue scale (VAS) from 0-100 where 0 = no HL and 100 = 100% HL. Assessments were every 2-3 weeks at the start of each CTX cycle, and once in follow-up 1-6 months after completing CTX. Additional data collected included pt reported adverse events and pt satisfaction with the success, ease of use, and tolerability of PCCT. Results: 31 pts (29 with ES and 2 with M disease) have registered. 25 have completed CTX and 20/25 are off study. 6 pts currently on CTX and 2 pts who stopped PCCT after cycle1 due to toxicity of CTX rather than issues with PCCT were excluded from the safety and efficacy analyses due to incomplete data. 2 additional pts were excluded from efficacy analysis due to beginning PCCT after the start of CTX, leaving 21 pts evaluable for efficacy and 23 pts for toxicity. CTX regimens included: docetaxel and cyclophosphamide (TC), docetaxel, carboplatin and trastuzumab (TCH), sequential doxorubicin and cyclophosphamide and paclitaxel, (AC/T), weekly nab-paclitaxel (nab). PCCT toxicities were all < grade 2 and included: 15 pts (71%) with headaches and 5 (22%) with dandruff during PCCT. All pts experienced head pain, and 20 pts (95%) had scalp pain and felt chilled during the PCCT. Table 1 depicts clinician and patient reported efficacy. Of the 20 pts assessed following completion of CTX and PCCT, 12 (60%) "highly recommend" PCCT, and 8 (40%) "recommend to some degree". No ESBC pts have worn a wig at any point. Conclusions: SC treatment (PCCT) is a viable but variably effective method of preventing HL for ESBC pts receiving CTX. The success of SC in hair preservation was dependent on the type and length of CTX regimen. Other patient factors impacting HL may exist. Short term toxicity is minimal. Given the emotional impact of CTX induced HL, ongoing study of PCCT and other SC devices, comparing different CTX regimens, is worthwhile. Ongoing studies at our center will include independently graded photographs to eliminate reporting bias by the clinician. Support for this trial was provided by the Tauber Foundation. [ABSTRACT FROM AUTHOR]

Background: GPNMB is an internalizable transmembrane glycoprotein overexpressed in multiple tumor types, including breast cancer (BC). GPNMB promotes BC metastases in a murine model and is a poor prognostic marker in patients (pts) (Rose 2010). CDX-011 (glembatumumab vedotin) is a fully human GPNMB-specific monoclonal antibody conjugated to the potent cellular toxin MMAE via a protease-sensitive peptide linker, designed to cleave upon cellular internalization. In Phase I/II studies of CDX-011 in BC (n = 42), an objective response rate (ORR) (including confirmed and unconfirmed response) of 12% overall and 20% for "triple-negative" (ER/PR/HER2-; TN) pts was observed (Saleh, ASCO 2010). Methods: The Phase II EMERGE study examined the efficacy of CDX-011 by level of GPNMB expression. Refractory BC (2-7 prior cytotoxic regimens in metastatic setting), GPNMB expression in ≥ 5% of tumor or stroma cells (as centrally determined on archival tumor), and no persistent treatment-related toxicity (including neuropathy) of ≥ Grade 2 severity were required for enrollment. Pts were stratified by GPNMB expression pattern (any tumor, low stromal or high stromal) and randomized 2:1 to CDX-011 (1.88 mg/kg IV q 21 days) or "investigator's choice" (IC) single-agent chemotherapy, and treated until progression (PD) or intolerance with IC pt crossover permitted to CDX-011 at PD. Endpoints: ORR (primary), progression-free survival (PFS), safety, pharmacokinetics, pharmacodynamics. Results: 99% of screened tumor samples expressed GPNMB. 122 treated pts (81 CDX-011 vs. 41 IC) had median age = 56 vs. 56 years; median # prior anticancer regimens = 6 vs. 5; visceral disease (liver/lung) = 83% vs. 80%; TN = 33% vs 27%, respectively. To date, 15 IC pts have crossed over to CDX-011, and 14 pts (8 CDX-011, 6 IC) continue on treatment. CDX-011 was well tolerated with less hematologic toxicity than IC; CDX-011-related toxicity included rash (overall = 38%; Grade 1 = 20%; Grade 2 = 15%; Grade 3 = 3%) and neuropathy (overall = 18%; Grade 1 = 8%; Grade 2 = 7%; Grade 3 = 2%). Conclusions: CDX-011 was a well-tolerated and active agent in this heavily pre-treated BC pt population. Preliminary analysis of the EMERGE study demonstrates enhanced activity of CDX-011 in TN as well as high GPNMB expressing BC tumors, confirming that CDX-011 is a targeted agent. This noted promising activity in advanced TN and hGPNMB enriched pt populations warrants further evaluation. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy, once reserved for locally advanced breast cancer, has become more common in Stage II disease. While one of its proven benefits is an increase in the frequency of breast conserving surgery, many women will undergo mastectomy despite an excellent clinical response. Indications for post-mastectomy radiation (PMRT) following neoadjuvant therapy are not well defined. Some studies have suggested that certain subgroups of women (young age, triple negative disease) with negative nodes or 1-3 positive nodes after chemotherapy have a significant risk of localregional failure without PMRT. We conducted a single-institution retrospective study of women undergoing neoadjuvant chemotherapy and mastectomy without PMRT to assess clinical outcomes among this cohort. Methods: 101 women with initial stage I-III disease (20% stage I, 72% stage II, 8% stage III) received neoadjuvant chemotherapy (doxorubicin-based +/- taxane) followed by mastectomy without PMRT between 2005 and 2011. Mean age was 49 years (range 22-81 years). 16% were BRCA+. 66 patients (65%) had clinically negative axillary nodes at presentation, 34% had N1 disease and 1% had N2 disease. Subtype by IHC was 61% luminal A, 11% luminal B (ER+, Her2+), 20% triple negative and 8% ER-, Her2+. At the time of surgery, 81% were node negative and 19% had 1-3 positive nodes. Pathologic complete response (pCR) (breast + axilla) occurred in 28%. Median follow-up was 34 months (range 5.5-84.5 months). Results: There were 2 (2%) local-regional failures (1 axillary recurrence at 52 months after mastectomy and 1 chest wall recurrence at 10 months). Both of these recurrences were in patients with negative nodes and luminal A tumors; patients had 2.2 and 2.5 cm of residual invasive cancer, respectively, and negative margins at mastectomy. There were no localregional failures in women with triple negative cancers, those with 1-3 positive nodes, or patients younger than 40. Additionally, there were no failures in women with a pCR, including those with initial stage IIIA-B disease. Conclusions: Among carefully selected patients fulfilling low risk criteria for local-regional recurrence, PMRT following neoadjuvant chemotherapy may be omitted without compromising local-regional control. [ABSTRACT FROM AUTHOR]

Background: Treatment options for human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases (BCBMs) remain limited. We previously reported central nervous system (CNS) activity for neratinib and neratinib-capecitabine. Preclinical data suggest that neratinib may overcome resistance to ado-trastuzumab emtansine (T-DM1) when given in combination. In Translational Breast Cancer Research Consortium (TBCRC) 022's cohort 4, we examined the efficacy of neratinib plus T-DM1 in patients with HER2-positive BCBM., Patients and Methods: In this multicenter, phase II study, patients with measurable HER2-positive BCBM received neratinib 160 mg daily plus T-DM1 3.6 mg/kg intravenously every 21 days in three parallel-enrolling cohorts [cohort 4A-previously untreated BCBM, cohorts 4B and 4C-BCBM progressing after local CNS-directed therapy without (4B) and with (4C) prior exposure to T-DM1]. Cycle 1 diarrheal prophylaxis was required. The primary endpoint was the Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) by cohort. The overall survival (OS) and toxicity were also assessed., Results: Between 2018 and 2021, 6, 17, and 21 patients enrolled in cohorts 4A, 4B, and 4C. Enrollment was stopped prematurely for slow accrual. The CNS objective response rate in cohorts 4A, 4B, and 4C was 33.3% [95% confidence interval (CI) 4.3% to 77.7%], 35.3% (95% CI 14.2% to 61.7%), and 28.6% (95% CI 11.3% to 52.2%), respectively; 38.1%-50% experienced stable disease for ≥6 months or response. Diarrhea was the most common grade 3 toxicity (22.7%). The median OS was 30.2 [cohort 4A; 95% CI 21.9-not reached (NR)], 23.3 (cohort 4B; 95% CI 17.6-NR), and 20.9 (cohort 4C; 95% CI 14.9-NR) months., Conclusions: We observed intracranial activity for neratinib plus T-DM1, including those with prior T-DM1 exposure, suggesting synergistic effects with neratinib. Our data provide additional evidence for neratinib-based combinations in patients with HER2-positive BCBM, even those who are heavily pretreated., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hepatitis C virus (HCV) infection often goes undiagnosed in asymptomatic carriers, but may become clinically relevant during periods of immunosuppression or severe illness. We report the clinical course of HCV reactivation in a patient receiving chemotherapy for metastatic colon cancer. We also review other reports showing the significance of HCV infection in patients being treated with chemotherapy.