Treatment-related hypomagnesemia and pertuzumab discontinuation in HER2-positive breast cancer: A decade of Appalachian data.

Abstract

e12677 Background: Breast cancer remains the most frequently diagnosed cancer among women. Intensive chemotherapy for early-stage HER2-positive breast cancer often causes side effects, including electrolyte disturbances. At our institution, treatment-related hypomagnesemia has become a notable concern, sometimes requiring interruption or adjustment of therapy. Despite the widespread use of these chemotherapy protocols, there are no established guidelines for routine magnesium monitoring. This study examined the frequency of hypomagnesemia, its association with specific chemotherapy regimens, and its impact on treatment completion. Methods: Our single-center retrospective study included adults with HER2-positive breast cancer treated from 2014 to 2024. We examined the frequency of hypomagnesemia during treatment for stage I-II HER2-positive breast cancer. Patients with preexisting hypomagnesemia were excluded. We also assessed the association between hypomagnesemia and standard chemotherapy regimens, including TCHP and TH. To minimize confounding, we adjusted analyses for diuretic and proton pump inhibitor (PPI) use. Secondary outcomes included rates and reasons for pertuzumab discontinuation in HER2-positive breast cancer, regardless of stage. Results: Among 138 early-stage HER2+ breast cancer patients without preexisting hypomagnesemia, 41.3% (57) developed hypomagnesemia during treatment. Hypomagnesemia was more common in patients receiving TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab) than in those receiving TH (paclitaxel, trastuzumab) (45.5% vs 23.1%, p = 0.036). After adjusting for potential confounders, including age, BMI, performance status, diuretic and PPI use, TCHP remained associated with higher odds of hypomagnesemia (OR 2.8, 95% CI 1.04–7.46; p = 0.04). This association was mediated mainly by diarrhea, which was strongly associated with hypomagnesemia (OR 4.54, 95% CI 2.04–10.12; p < 0.001). Across all stages of HER2+ breast cancer (134), the pertuzumab discontinuation rate was 46.3% (62), with diarrhea accounting for the majority of discontinuations (64%). Conclusions: TCHP therapy is associated with an increased risk of hypomagnesemia, primarily due to treatment-related diarrhea, which often leads to discontinuation of treatment. Larger prospective studies are needed to assess the clinical significance. Patients receiving pertuzumab-based therapy may benefit from regular magnesium monitoring and early intervention. Comparison of Hypomagnesemia and Diarrhea outcomes between TCHP and HP regimens. Outcome TCHP (112) TH (26) Estimate Hypomagnesemia, n (%) 45.5% 23.1% p = 0.036 Diarrhea, n (%) 56.3% 3.9% p < 0.001 Median days to hypomagnesemia (IQR) 63 (41–92) 42 (14–73) p = 0.34 TCHP vs TH (adjusted OR, 95% CI) — — 2.79 (1.04–7.46) Diarrhea (adjusted OR, 95% CI) — — 4.54 (2.04–10.12)