Long-term follow-up of early stage HER2-positive breast cancer patients treated with trastuzumab: A population-based real world multicenter cohort study

Abstract

IntroductionSince its introduction in standard of care, trastuzumab has revolutionized the treatment of patients with early and late stages of HER2-positive breast cancer. While the initial clinical trials were convincing and lead to major changes in practice, more knowledge on the long-term outcome and tolerability is needed. The present study was designed to assess the survival, prognostic factors and relapse patterns after the implementation of trastuzumab in a real-world cohort.MethodsAll cases of HER2-positive breast cancer diagnosed between 2006 and 2014 in the Southeast Healthcare Region of Sweden were retrospectively identified. Medical records were thoroughly reviewed with regard to clinicopathological parameters, treatments, relapse pattern and adverse events.Results643 patients were identified and 599 were eligible for analysis. Breast cancer specific survival, distant recurrence free survival and local recurrence free survival were 93.4%, 89.7% and 98.0% for trastuzumab treated patients and 87.4%, 81.6% and 87.4% in patients not treated with trastuzumab, respectively. ER status, nodal status and trastuzumab treatment were all independent prognostic factors in multivariable analysis. No new safety concerns were discovered.ConclusionThe real-world outcome of trastuzumab-treated patients with early HER2-positive breast cancer is similar to what has been previously reported in long-term follow up of prospective clinical trials. ER status, nodal status and trastuzumab treatment are independent prognostic factors for breast cancer specific mortality rate, distant recurrence rate and locoregional recurrence rate in HER2-positive patients in the trastuzumab era.

Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes

“…Nevertheless, HER2 status interpretation, and subsequently, an accurate classification of BC patients, can be affected by several factors, with HER2 heterogeneity being the most important one, as documented elsewhere for other neoplasms [33,41,42]. In fact, In clinical practice, these guidelines have been used to discriminate HER2-negative BCs from HER2-positive BCs, the latter being eligible for target therapy with anti-HER2 monoclonal antibodies, such as trastuzumab, pertuzumab, and margetuximab, which are able to improve the clinical outcomes of these tumors [23][24][25][35][36][37]. However, only 20% of BCs are HER2-positive, leaving the rest with fewer treatment options, confined to endocrine therapy and/or chemotherapy with less clinical benefits and more side effects [38][39][40].…”

“…Obviously, the ISH rejection criteria have to be applied in a rigorous fashion in all BC cases (Table 2). In clinical practice, these guidelines have been used to discriminate HER2-negative BCs from HER2-positive BCs, the latter being eligible for target therapy with anti-HER2 monoclonal antibodies, such as trastuzumab, pertuzumab, and margetuximab, which are able to improve the clinical outcomes of these tumors [23][24][25][35][36][37]. However, only 20% of BCs are HER2-positive, leaving the rest with fewer treatment options, confined to endocrine therapy and/or chemotherapy with less clinical benefits and more side effects [38][39][40].…”

“…In fact, HER2 overexpression is present in approximately 20% of patients with BC [ 19 ], and it is usually associated with more aggressive behavior [ 20 ], a higher risk of disease recurrence, and a shorter OS [ 20 , 21 , 22 ] in comparison to HER2-negative (HER2-) BCs. To date, no effective target treatments have been approved for HER2-negative BC patients, since several studies have demonstrated a beneficial effect of the addition of trastuzumab to chemotherapy only in tumors with HER2 overexpression [ 23 , 24 , 25 ]. However, recently, the introduction of novel anti-HER2 antibody–drug conjugates (ADC) strategies showed promising response rates and progression-free survival (PFS) in the so-called HER2-“low” BCs, a new definition attributed to tumors which present an HER2 IHC score of 1+ or 2+ without HER2 amplification [ 26 , 27 , 28 ].…”

Modern Management and Diagnostics in HER2+ Breast Cancer with CNS Metastasis

“…Since the advent of Trastuzumab in the late twentieth century, prognosis of HER2+ breast cancer has improved significantly by measure of overall survival (OS), progressionfree survival (PFS), and recurrence-free survival [47]. However, prognosis among all patients with breast cancer with metastases to the brain remains poor, with survival of about 3-36 months [48].…”

Epidemiology trends and progress in breast cancer survival: earlier diagnosis, new therapeutics

“…The evidence on the impact of systemic, adjuvant therapies is mainly for anti-HER2 or endocrine treatments. Studies from Canada and Sweden using data from the real-world setting found that anti-HER2 targeted agents led to survival improvements for women with HER2-positive early BC, with 5-year BC-specific survival of 93% versus 87% for patients receiving or not receiving adjuvant trastuzumab in 2006–2014, respectively [ 10 ▪ , 55 ].…”