Tumour Review
Time for more optimism in metastatic breast cancer?

https://doi.org/10.1016/j.ctrv.2013.09.015Get rights and content

Abstract

Treatment of metastatic breast cancer has substantially changed in the last decades. Availability of new cytotoxics and targeted therapies as well as changes in treatment philosophy and strategy have all contributed to a significant improvement in both survival and patients’ quality of life. The multidisciplinary approach, personalised treatments based on tumour characteristics, patient’s and disease history, as well as re-definition of treatment goals, aiming at the lowest possible impact on patients’ life by replacing aggressive multidrug chemotherapy with single-agent cytotoxic treatment or endocrine ± targeted therapies, have all been the bases of the new treatment paradigm. More recently the development of the international advanced breast cancer (ABC) consensus guidelines have further contributed to this improvement. This review will focus on the major achievements and challenges in the different tumour subtypes and sites, with a focus on future research topics and trends.

Introduction

Breast cancer (BC) is the most prevalent female malignancy and the second most common cause of death in developed countries. In 2013 in the United States, an estimated 234,580 women will be diagnosed with invasive BC and 40,030 will die from it [1]. In 2008, in Europe there were 424,800 new BC cases and 128,700 BC-related deaths [2]. Every year almost half a million women lose their lives to breast cancer [2]. Recent years have faced remarkable changes both in the treatment philosophy of metastatic breast cancer (MBC) and in the available therapies, contributing to improvements in survival rates and quality of life.

BC is a heterogeneous disease, characterised by deregulation of multiple cellular pathways, different morphology and sensitivity to various treatments. Better understanding of BC biology has led to targeted treatments against specific molecular subsets, resulting in improved outcomes. In a large single-institution retrospective study of 2091 women, after adjusting for patient and tumour characteristics, women with HER2+/ER+(luminal HER2+) disease treated with trastuzumab had 5 years’ survival similar to those with HER2-/ER+(luminal HER2−) tumours (29.7% vs. 31.3%, respectively), while the 5 years’ survival of women with luminal HER2+ disease who did not receive trastuzumab was significantly worse (14.5%) and similar to trastuzumab-treated women with HER2+/ER− disease (17.7%). Finally, women with HER2+/ER− disease who did not receive trastuzumab had only 8.9% 5 years’ survival, similar to that of triple negative (TN) patients (7.9%) [3].

Breast cancer subtypes also differ by the pattern of metastatic disease. In a large series of 3726 early BC patients from British Columbia bone was the most common metastatic site in all subtypes except basal-like tumours. Compared with luminal HER2−, luminal HER2+ and HER2+/ER− tumours were associated with significantly more brain, liver, and lung metastases, whereas basal-like tumours had higher rate of brain, lung, and distant nodal metastases but significantly less liver and bone metastases [4]. A strikingly high tendency of TN cancers to metastasize to brain was also seen in other series [5], [6], whereas luminal B tumours seem to be related to higher risk of bone metastases [7]. Median survival was dependent on the tumour subtype and ranged from 0.5 years for basal-like to 2.2 years for luminal HER2− tumours (p < 0.001) [4]. Several studies have also demonstrated significant differences in the timing of distant recurrence: oestrogen receptor negative (ER−) tumours tend to be associated with early relapse whereas ER+ tumours show a persistent late risk beyond 5 years [8], [9], [10]. In the British Columbia population, although at the 5-year time point HER2+/ER− patients had significantly higher relapse rate than luminal HER2+ tumours, this difference was lost at 15 years as a result of more late relapses in the latter group [4].

Selecting therapies in MBC requires therefore consideration not only of patient status and disease extent but also of the tumour molecular characteristics, defined by either genomic testing [11] or immunohistochemistry [12], [13], [14]. When considering survival improvements and potential areas of progress in MBC it is hence crucial to analyse each disease subtype separately.

Section snippets

Endocrine responsive (luminal) breast cancer

Luminal HER2-negative BC represents 60–65% of all newly diagnosed patients. Although prognosis in this subtype is generally good, still many women will relapse and luminal HER2-negative BC remains the most common subtype among MBC patients.

Conclusion

In spite of all the developments and the huge progress in our understanding of BC behaviour, MBC still remains an incurable disease, and still too few patients can be turned to a chronic, long-lasting condition. Apart from limitations related to disease biology, professionals caring for MBC patients face many (often unnecessary and avoidable) organizational and economic obstacles [140]. Additionally, in contrast to early BC, management of MBC is less frequently based on local or international

Conflict of interest statement

E. Senkus has reported advisory board for GlaxoSmithKline and AstraZeneca; travel support from Roche and Amgen. F. Cardoso has reported consultancy/research grants from Eisai, Roche, GlaxoSmithKline, Celgene, AstraZeneca, Novartis, Pfizer, Astellas, GE Oncology, Merck-Sharp, Merus, BV, Genentech; speaker’s bureau from Novartis, GlaxoSmithKline. O. Pagani has reported no conflict of interest.

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