Estrogen/progesterone receptor and HER2 discordance between primary tumor and brain metastases in breast cancer and its effect on treatment and survival

Abstract

Background Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM). Methods A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the BCBM. Results The overall receptor discordance rate was 132/316 (42%), and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors—nonetheless, median survival (MS) improved but did not reach statistical significance (HR, 17–28 mo, P = 0.12; HER2, 15–19 mo, P = 0.39). MS for patients who lost receptors was worse (HR, 27–18 mo, P = 0.02; HER2, 30–18 mo, P = 0.08). Conclusions Receptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost, and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly. Key Points 1. Receptor discordance alters subtype in 32% of BCBM patients. 2. The frequency of receptor gain for HR and HER2 was 25% and 13%, respectively. 3. If receptors are lost, survival suffers. If receptors are gained, consider targeted treatment.

Estrogen, progesterone, and human epidermal growth factor receptor 2 discordance between primary and metastatic breast cancer

“…In our collective, antiendocrine treatment was subject to change in 20% of patients and HER2-directed treatment in 14% of patients before and after metastasis biopsy. This is in line with previously reported fractions of 18–57% and 7–50% in other cohorts ( [ 43 – 47 ]). Concluding, it is clinically relevant to detect changes in receptor status in the metastatic setting in order to tailor therapeutic interventions according to present tumor manifestation.…”

Systematic review and meta-analysis of breast cancer brain metastasis and primary tumor receptor expression discordance

“…The data from this study suggest that perhaps up to 10% of these patients could have been found to be HER2+ and could potentially have benefitted from a change in the therapeutic regimen. 28 Given the increasing availability of HER-2 directed therapeutic options for patients with BCBM with intracranial response rates of 50–66%, 40–43 as well as the evidence of the importance of timing these agents with SRS, 44 tumor receptor expression analysis is recommended to be performed on all biopsied or resected BCBM, with specific inclusion of retesting HER2. Whether this practice change translates into an actual survival benefit could only be determined by a large randomized prospective trial.…”

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

“…Adding complexity to SACT options for these patients is the not rare event of discordance in hormone receptor status between primary tumor and CNS metastasis, with an HR+ primary switching to negative in one-fifth to one-third of cases [ 72 , 73 , 82 ]. New diagnostic techniques, such as analysis of circulating epithelial tumor cell DNA in CSF, could help increase diagnostic sensitivity and specificity and establish ABC subgroups as well as driver and resistance mutations, which could help dictate therapeutic choices [ 83 ].…”

“…In all retrospective studies analyzed, the trend is the same, whenever SACT is used, ET is not the first choice and we cannot assure that this happens due to endocrine resistance or lack of available lines. We speculate that clinicians consider that ET is not a suitable option for CNS metastasis [67] and opt for ITT or chemotherapy, even if CNS metastasis remains HR+ in more than two thirds of patients [71][72][73]. Furthermore, underlined studies were performed in very uneven time periods and thus a great heterogeneity in treatment approaches can be observed, reflecting the great changes that ABC treatment has undergone in the last decades yet missing the advent of the CDK 4/6 inhibitors era.…”