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Observational Study
. 2016 Apr 5;7(14):17932-44.
doi: 10.18632/oncotarget.7480.

"Triple positive" early breast cancer: an observational multicenter retrospective analysis of outcome

Patrizia Vici  1 , Laura Pizzuti  1 , Isabella Sperduti  2 , Antonio Frassoldati  3 , Clara Natoli  4 , Teresa Gamucci  5 , Silverio Tomao  6 , Andrea Michelotti  7 , Luca Moscetti  8 , Stefania Gori  9 , Editta Baldini  10 , Francesco Giotta  11 , Alessandra Cassano  12 , Daniele Santini  13 , Diana Giannarelli  2 , Luigi Di Lauro  1 , Domenico Cristiano Corsi  14 , Paolo Marchetti  15 , Valentina Sini  15   16 , Domenico Sergi  1 , Maddalena Barba  1   17 , Marcello Maugeri-Saccà  1   17 , Michelangelo Russillo  10 , Lucia Mentuccia  5 , Loretta D'Onofrio  13 , Laura Iezzi  4 , Angelo Fedele Scinto  14 , Lucia Da Ros  3 , Ilaria Bertolini  7 , Maria Luisa Basile  18 , Valentina Rossi  19   20 , Ruggero De Maria  17 , Filippo Montemurro  19
Affiliations
Observational Study

"Triple positive" early breast cancer: an observational multicenter retrospective analysis of outcome

Patrizia Vici et al. Oncotarget. .

Abstract

We recently found that trastuzumab benefit may be lower in a small subset of early breast cancer (BC) patients (pts) with tumors expressing high levels of both hormonal receptors (HRs), i.e. triple positive (TP). To better investigate the role of HRs in HER2 positive BC, we retrospectively identified 872 TP BC pts treated with adjuvant chemotherapy alone (cohort A-366 pts), or plus trastuzumab (cohort B-506 pts). Relapse-free-survival (RFS) and breast-cancer-specific-survival (BCSS) were evaluated. Trastuzumab improved RFS and BCSS in all the subsets analyzed, but the effect on BCSS in tumors expressing both HRs in >30% of cells (TP30), and even on RFS in tumors with both HRs expressed in >50% of cells (TP50) was not significant. Distinct patterns of relapse were observed in TP50 and no-TP50 tumors, the former showing low and constant risk in the first 5 years, a late increase beyond 5 years and modest trastuzumab effect. Trastuzumab effect tended to disappear in pts whose tumors expressed ER in >50% of cells. Multivariate analysis of RFS confirmed a significant interaction between trastuzumab and ER expression, with benefit confined to pts whose tumors expressed ER in ≤50% of cells. Our data suggest that the pattern of relapse of TP tumors with high HRs is similar to that of "luminal", HER2 negative tumors, without clear benefit from adjuvant trastuzumab, which remains the standard treatment even in TP tumors. Confirmatory findings on the extent to which quantitative expression of HRs may impact clinical behavior of HER2 positive BC are warranted.

Keywords: adjuvant breast cancer; chemotherapy; hormonal receptors; trastuzumab; triple positive.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Relapse-free survival (1) and breast cancer specific survival (2) in the overall study population (N=872) according to cohort
Abbreviations: RFS, relapse free survival; BCSS, breast cancer specific survival. Cohort A: red line; Cohort B: blue line.
Figure 2
Figure 2. Hazard rate of recurrence for the overall study population (panel A) and in patients with ER and PgR staining in more than 50% of tumour cells (TP50, panel B) and other patients (noTP50, panel C)
Cohort A: red line; Cohort B: blue line.
Figure 3
Figure 3. Stepp analysis of the effect on ER (Panel A) and PgR (Panel B) expression on the hazard of relapse in the two cohorts
Abbreviations: ER, estrogen receptor; PgR, progesterone receptor; RFS, relapse free survival.
See this image and copyright information in PMC

References

    1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–182. - PubMed
    1. Lal P, Tan LK, Chen B. Correlation of HER-2 status with estrogen and progesterone receptors and histologic features in 3,655 invasive breast carcinomas. Am J Clin Pathol. 2005;123:541–546. - PubMed
    1. Cortés J, Saura C, Bellet M, Muñoz-Couselo E, Ramírez-Merino N, Calvo V, Pérez J, Vidal M. HER2 and hormone receptor-positive breast cancer--blocking the right target. Nat Rev Clin Oncol. 2011;8:307–311. - PubMed
    1. Untch M, Fasching PA, Konecny GE, Hasmüller S, Lebeau A, Kreienberg R, Camara O, Müller V, du Bois A, Kühn T, Stickeler E, Harbeck N, Höss C, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011;29:3351–3357. - PubMed
    1. Moja L, Tagliabue L, Balduzzi S, Parmelli E, Pistotti V, Guarneri V, D'Amico R. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev. 2012;4:CD006243. - PMC - PubMed

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