Response of Brain Metastases From <i>PIK3CA</i>-Mutant Breast Cancer to Alpelisib

Background. Breast cancer is the most common cancer among women worldwide, and the second leading cause of brain metastases (BrM). We assessed the treatment patterns and outcomes of women treated for breast cancer BrM at our institution in the modern era of stereotactic radiosurgery (SRS). Materials and Methods. We conducted a retrospective analysis of women (≥ 18 years old) with metastatic breast cancer who were treated with surgery, whole brain radiotherapy (WBRT) or SRS to the brain at the Sunnybrook Odette Cancer Center, Toronto, Canada between 2008 and 2018. Patients with a history of other malignancies and those with an uncertain date of diagnosis of BrM were excluded. Descriptive statistics were generated and survival analyses were performed, with subgroup analyses by breast cancer subtype.Results. Among 683 eligible patients, 153 (22.4%) had triple negative (TNBC), 188 (27.5%) had HER2+, 246 (36.0%) had hormone receptor (HR)+/HER2-, and 61 (13.3%) had breast cancer of unknown subtype. The majority of patients received fist line WBRT (n=459, 67.2%) or SRS (n=126, 18.4%). The median brain-specific progression-free survival and median overall survival (OS) were 4.1 months (IQR 1.0-9.6 months) and 5.1 months (IQR 2.0-11.7 months) in the overall patent population, respectively. Age >60 years, presence of neurological symptoms at BrM diagnosis, first line WBRT and HER2-subtype were independently prognostic for shorter OS. Conclusion. Despite the use of SRS, outcomes among patients with breast cancer BrM remain poor. Strategies for early detection of BrM and central nervous system-active systemic therapies warrant further investigation. The Oncologist 2021;9999:• • Implications for Practice: Although triple negative and HER2+ breast cancer have a predilection for metastasis to the central nervous system (CNS), patients with hormone receptor (HR)+/HER2-breast cancer represent a high proportion of patients with breast cancer brain metastases (BrM). Hence, clinical trials should include patients with BrM and evaluate CNS-specific activity of novel systemic therapies when feasible, irrespective of breast cancer subtype. In addition, given that symptomatic BrM are associated with shorter survival, we propose that screening programs for the early detection and treatment of breast cancer BrM warrant further investigation in an era of minimally toxic stereotactic radiosurgery.

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“…Breast cancer brain metastases cohort study [57,58] in combination with endocrine therapy have already shown promising CNS-specific activity.…”

Section: Discussionmentioning

confidence: 99%

Treatment Patterns and Outcomes of Women with Symptomatic and Asymptomatic Breast Cancer Brain Metastases: A Single-Center Retrospective Study

et al. 2021

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“…Also, regarding mTOR/AKT/PI3K inhibitors, it seems that PI3K-mutant patients have a higher probability of developing CNS metastasis [ 79 , 80 ], which is something that requires further exploration in BC-LMD [ 76 ]. Specifically, as identified by Le Rhun et al , single nucleotide polymorphisms in the PI3KR1 gene seem to be associated with CNS metastasis [ 79 ].…”

Section: Discussionmentioning

confidence: 99%

“…With the introduction of CDK4/6 and mTOR/AKT/PI3K inhibitors, more therapeutic options for luminal ABC are available, which can somewhat overcome this problem. Palbociclib, abemaciclib, everolimus and buparlisib are all able to cross the BBB [7,26,65,66,75], and alpelisib appears to be active against parenchymal brain metastasis [76].…”

Section: Endocrine Therapy Combined With Other Agentsmentioning

confidence: 99%

Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review

et al. 2020

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Leptomeningeal disease (LMD) represents a devastating complication of advanced breast cancer (ABC), with survival of <5 months with multimodal treatment. The role of endocrine therapy (ET), due to its favorable toxicity profile and first-line indication in luminal ABC, appears promising in the setting of LMD, where symptom stabilization and quality-of-life preservation are the main goals; however, evidenced-based data are lacking. We conducted a thorough review of published evidence, aiming to investigate the role of ET in LMD treatment in luminal ABC. Twenty-one of 342 articles, evaluating 1302 patients, met inclusion criteria. ET use was rarely reported. New targeted agents show CNS activity. Research is lacking on the role of ET and targeted agents in BC-LMD treatment.

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“… 30 Preclinical and clinical data further support that PIK3CA inhibitors have clinical efficacy in BM. 31 , 32 , 33 Further, molecular research focusing specifically on molecular drivers could reveal targets for targeted treatment approaches.…”

Section: Discussionmentioning

confidence: 99%

Primary tumor side is associated with prognosis of colorectal cancer patients with brain metastases

et al. 2021

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Background Brain metastases (BM) are a rare complication in colorectal cancer (CRC) patients and associated with an unfavorable survival prognosis. Primary tumor side (PTS) was shown to act as a prognostic and predictive biomarker in several trials including metastatic CRC (mCRC) patients. Here, we aim to investigate whether PTS is also associated with the outcome of CRC patients with BM. Methods Patients treated for CRC BM between 1988 and 2017 at an academic care center were included. Right-sided CRC was defined as located in the appendix, cecum and ascending colon and left-sided CRC was defined as located in the descending colon, sigma and rectum. Results Two hundred and eighty-one CRC BM patients were available for this analysis with 239/281 patients (85.1%) presenting with a left-sided and 42/281 patients (14.9%) with a right-sided primary CRC. BM-free survival (BMFS) was significantly longer in left-sided compared with right-sided CRC patients (33 versus 20 months, P = 0.009). Overall survival from CRC diagnosis as well as from diagnosis of BM was significantly longer in patients with a left-sided primary (42 versus 25 months, P = 0.002 and 5 versus 4 months, P = 0.005, respectively). In a multivariate analysis including graded prognostic assessment, PTS remained significantly associated with prognosis after BM (hazard ratio 0.65; 95% confidence interval: 0.46-0.92 months, P = 0.0016). Conclusions PTS was associated with survival times after the rare event of BM development in CRC patients. Therefore, its prognostic value remains significant even thereafter.

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Response of Brain Metastases From PIK3CA-Mutant Breast Cancer to Alpelisib

Cited by 35 publications

References 24 publications

Treatment Patterns and Outcomes of Women with Symptomatic and Asymptomatic Breast Cancer Brain Metastases: A Single-Center Retrospective Study

Treatment Patterns and Outcomes of Women with Symptomatic and Asymptomatic Breast Cancer Brain Metastases: A Single-Center Retrospective Study

Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review

Primary tumor side is associated with prognosis of colorectal cancer patients with brain metastases

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