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. 2023 Apr 6;25(1):36.
doi: 10.1186/s13058-023-01632-5.

Clinical evaluation of molecular surrogate subtypes in patients with ipsilateral multifocal primary breast cancer

Slavica Janeva  1   2 , Ellen Krabbe  3 , Toshima Z Parris  4   5 , Salmir Nasic  6   7 , Marie Sundquist  8 , Per Karlsson  4   9 , Riccardo A Audisio  10   11 , Roger Olofsson Bagge  10   5   11   12 , Anikó Kovács  13   14
Affiliations

Clinical evaluation of molecular surrogate subtypes in patients with ipsilateral multifocal primary breast cancer

Slavica Janeva et al. Breast Cancer Res. .

Abstract

Background: When ipsilateral multifocal primary breast cancer (IMBC) is detected, standard routine is to evaluate the largest tumor with immunohistochemistry (IHC). As all foci are not routinely characterized, many patients may not receive optimal adjuvant treatment. Here, we assess the clinical relevance of examining at least two foci present in patients with IMBC.

Methods: Patients diagnosed and treated for IMBC at Sahlgrenska University Hospital (Gothenburg, Sweden) between 2012 and 2017 were screened. In total, 180 patients with ≥ 2 invasive foci (183 specimens) were assessed with IHC and included in this study. Expression of the estrogen (ER) and progesterone (PR) receptors, Ki67, HER2, and tumor grade were used to determine the molecular surrogate subtypes and discordance among the foci was recorded. An additional multidisciplinary team board was then held to re-assess whether treatment recommendations changed due to discordances in molecular surrogate subtype between the different foci.

Results: Discordance in ER, PR, HER2, and Ki67 was found in 2.7%, 19.1%, 7.7%, and 16.9% of invasive foci, respectively. Discordance in the molecular surrogate subtypes was found in 48 of 180 (26.7%) patients, which resulted in therapy changes for 11 patients (6.1%). These patients received additional endocrine therapy (n = 2), chemotherapy (n = 3), and combined chemotherapy and trastuzumab (n = 6).

Conclusion: Taken together, when assessing at least two tumor foci with IHC, regardless of shared morphology or tumor grade between the different foci, 6.1% of patients with IMBC were recommended additional adjuvant treatment. A pathologic assessment using IHC of all foci is therefore recommended to assist in individualized treatment decision making.

Keywords: Adjuvant treatment; Biomarkers; Breast cancer subtypes; Discordant; Multicentric breast cancer; Multifocal breast cancer; Synchronous.

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Conflict of interest statement

The authors SJ, EK, TZP, SN, MS and RAA declare no conflict of interest. PK reports Research Contract Prelude DX and PFS genomics and has advisory role in AstraZeneca. ROB has received institutional research grants from Bristol-Myers Squibb (BMS), Endomagnetics Ltd (Endomag) and SkyLineDx, speaker honorarium from Roche, Pfizer and Pierre-Fabre, and has served on advisory boards for Amgen, BD/BARD, Bristol-Myer Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Roche and Sanofi Genzyme, and is as shareholder in SATMEG Ventures AB. AK has received honorarium from Roche, MSD and Pfizer and is a member of the Advisory Board of Pfizer.

Figures

Fig. 1
Fig. 1
Flowchart of patients with ipsilateral multifocal breast cancer surgically treated at Sahlgrenska University Hospital (Gothenburg, Sweden) during 2012–2017
Fig. 2
Fig. 2
Clinical relevance of therapeutic changes due to discordance in molecular surrogate subtypes in the largest tumor (PT1) and the second tumor (PT2) in 11 of 180 patients with ipsilateral multifocal primary breast cancer that were surgically treated at Sahlgrenska University Hospital (Gothenburg, Sweden) between 2012 and 2017
Fig. 3
Fig. 3
In total, 103 specimens with matching histologic type and grade (NHG) between the largest primary tumor (PT1) and second primary tumor (PT2) assessed with immunohistochemistry in specimens with ipsilateral multifocal primary breast cancer
Fig. 4
Fig. 4
Comparison between concordant with discordant molecular surrogate subtypes for A disease-free survival (DFS) and B overall survival (OS) in patients with ipsilateral multifocal primary breast cancer (IMBC) surgically treated at Sahlgrenska University Hospital (Gothenburg, Sweden) between 2012 and 2017. One patient with IMBC was excluded from the analysis since the left-side specimen had concordant subtypes, while the right-side specimen had discordant subtypes between the different foci. This patient had no events
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