Abstract
PIK3CA mutation frequency varies among breast cancer (BC) subtypes. Recent evidence suggests combination therapy with the PI3K inhibitor (PI3Ki) alpelisib and endocrine therapy (ET) improves response rates and progression-free survival (PFS) in PIK3CA-mutant, hormone receptor positive (HR+) BC versus ET alone; thus, better understanding the clinical and epidemiologic elements of these mutations is warranted. This systematic review characterizes the PIK3CA mutation epidemiology, type of testing approaches (e.g., liquid or tissue tumor biopsy), and stability/concordance (e.g., consistency in results by liquid versus solid tumor sample, by the same method over time) in patients with HR+/HER2– advanced (locally unresectable) or metastatic disease (HR+/HER2– mBC) and explores performance (e.g., pairwise concordance, sensitivity, specificity, or predictive value) of respective mutation findings. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts (i.e., AACR, ASCO, SABCS, ECCO, and ESMO conferences between 2014 and 2017) identified 39 studies of patients with HR+, HER2– mBC. The median prevalence of PIK3CA mutation was 36% (range: 13.3% to 61.5%); identified testing approaches more commonly used tissue over liquid biopsies and primarily utilized next-generation sequencing (NGS), polymerase chain reaction (PCR), or Sanger sequencing. There was concordance and stability between tissues (range: 70.4% to 94%) based on limited data. Given the clinical benefit of the PI3Ki alpelisib in patients with PIK3CA mutant HR+/HER2– mBC, determination of tumor PIK3CA mutation status is of importance in managing patients with HR+/HER2– mBC. Prevalence of this mutation and utility of test methodologies likely warrants PIK3CA mutation testing in all patients with this breast cancer subtype via definitive assessment of PIK3CA mutational status.
Highlights
With an estimated 271,270 new cases in 2019, breast cancer (BC) is the most common nonskin cancer in women in the United States (US) [1]
A total of 6825 nonduplicated individual samples were tested for genetic mutations including PIK3CA
The results of SOLAR-1 highlight the tangible benefit of testing for PIK3CA mutations in patients with HR+/HER2mBC, an approach recommended by the National Comprehensive Cancer Network (NCCN) consensus guidelines as well [8]
Summary
With an estimated 271,270 new cases in 2019, breast cancer (BC) is the most common nonskin cancer in women in the United States (US) [1]. Most BC cases are diagnosed in the early stages, approximately 10 to 41% of patients develop metastatic or advanced (locally unresectable; stage 3 or 4) disease, depending on tumor characteristics and presentation [2]. The phosphoinositide 3-kinase (PI3K) pathway is the most frequently altered pathway in HR+ BC and is associated with tumor development, disease progression, and endocrine resistance [4]. The impact of PIK3CA mutation status on BC progression (e.g., localized to metastatic disease) is uncertain [5]. Current treatment options for postmenopausal HR+/HER2advanced BC include endocrine therapy (ET) +/- a CDK 4/6 inhibitor, an mTOR inhibitor, or chemotherapy (CT) [6]. ET or TT+ET rather than chemotherapy constitutes the initial therapy usually administered for women with HR+ advanced BC; TT+ET has more manageable safety profiles than CT [7].
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