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The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial.

ABSTRACT: In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world setting at 45 Italian cancer centers were retrospectively collected and analyzed. From 2003 to 2017, 491 HER2-positive mBC patients were included. Of these, 102 (20.7%) had been initially diagnosed as HER2-negative early BC. Estrogen and/or progesterone receptor were more expressed in patients with HER2-discordance compared to patients with HER2-concordant status (p < 0.0001 and p = 0.006, respectively). HER2-discordant tumors were characterized also by a lower rate of brain metastases (p = 0.01) and a longer disease free interval (p < 0.0001). Median overall survival was longer, although not statistically significant, in the subgroup of patients with HER2-discordant cancer with respect to patients with HER2-concordant status (140 vs 78 months, p = 0.07). Our findings suggest that patients with HER2-positive mBC with discordant HER2 status in early BC may have different clinical, biological and prognostic behavior compared to HER2-concordant patients.

SUBMITTER: Pizzuti L

PROVIDER: S-EPMC8253801 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial.

Pizzuti Laura L Barba Maddalena M Mazzotta Marco M Krasniqi Eriseld E Maugeri-Saccà Marcello M Gamucci Teresa T Berardi Rossana R Livi Lorenzo L Ficorella Corrado C Natoli Clara C Cortesi Enrico E Generali Daniele D La Verde Nicla N Cassano Alessandra A Bria Emilio E Moscetti Luca L Michelotti Andrea A Adamo Vincenzo V Zamagni Claudio C Tonini Giuseppe G Sergi Domenico D Marinelli Daniele D Paoletti Giancarlo G Tomao Silverio S Botticelli Andrea A Marchetti Paolo P Tinari Nicola N Grassadonia Antonino A Valerio Maria Rosaria MR Mirabelli Rosanna R Fabbri Maria Agnese MA D'Ostilio Nicola N Veltri Enzo E Corsi Domenico D Garrone Ornella O Paris Ida I Sarobba Giuseppina G Meattini Icro I Pistelli Mirco M Giotta Francesco F Lorusso Vito V Garufi Carlo C Russo Antonio A Cazzaniga Marina M Del Medico Pietro P Roselli Mario M Vaccaro Angela A Perracchio Letizia L di Benedetto Anna A Daralioti Theodora T Sperduti Isabella I De Maria Ruggero R Di Leo Angelo A Sanguineti Giuseppe G Ciliberto Gennaro G Vici Patrizia P

Scientific reports 20210702 1

In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world settin ...[more]

PMID: 34215766

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Project description:BackgroundLoss of HER2 "positivity" can occur in patients with residual disease after neoadjuvant treatment, but the incidence of HER2-positivity loss after neoadjuvant dual HER2-targeted treatment plus chemotherapy, the current standard-of-care for most early stage HER2-positive breast cancers, is not well described. Previous studies that report the HER2 discordance rate after neoadjuvant treatment also do not include the novel HER2-low category. In this retrospective study, we determine the incidence and prognostic impact of HER2-positivity loss, including the evolution to HER2-low disease, after neoadjuvant dual HER2-targeted therapy with chemotherapy.MethodsClinicopathologic data for patients with stage I-III HER2+ breast cancer diagnosed between 2015 and 2019 were reviewed in this single institution retrospective study. Patients who received dual HER2-targeted treatment with chemotherapy were included, and HER2 status before and after neoadjuvant therapy was interrogated.ResultsA total of 163 female patients were included in the analysis with a median age of 50 years. A pathologic complete response (pCR as defined by ypT0/is) was achieved in 102 (62.5%) of 163 evaluable patients. Among the 61 patients with residual disease after neoadjuvant therapy, 36 (59.0%) had HER2-positive and 25 (41.0%) had HER2-negative residual disease. Of the 25 patients with HER2-negative residual disease, 22 (88%) of patients were classified as HER2-low. After a median follow-up of 3.3 years, patients who retained HER2-positivity after neoadjuvant treatment had a 3-year IDFS rate of 91% (95% CI, 91%-100%), while patients who lost HER2-positivity had a 3-year IDFS rate of 82% (95% CI, 67%-100%).ConclusionAlmost half of patients with residual disease following neoadjuvant dual HER2-targeted therapy plus chemotherapy lost HER2-positivity. The loss of HER2-positivity may not confer negative prognostic impact, although the results were limited by short follow-up time. Further research on the HER2 status after neoadjuvant treatment may help guide treatment decisions in the adjuvant setting.

Dataset Information

The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial.

Publications

The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial.

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