Latest Approaches to Loco-Regional and Systemic Therapies for Breast Cancer

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Background

Despite an upward trend in incidence of breast cancer among women in the Western world, mortality rates have fallen over the past two decades and 10 year survival rates for many leading centres exceed 80%. This is testimony to interventional strategies such as screening and adjuvant systemic therapies that permit diagnosis and initiation of treatment prior to formation of metastases at distant sites. This burden of micrometatastic disease beyond the breast and regional tissues represents the most challenging aspect of breast cancer treatment. Nonetheless, prevention of local recurrence can save lives, local control does matter and rates of local recurrence should be minimised in the first 5 years. This principle applies to reduction in local relapse from both adjuvant radiotherapy and surgical modalities.

This Research Topic will focus on frontiers in breast cancer treatment and consider the latest approaches to both loco-regional and systemic therapies. In addition, a section on breast cancer screening for both average and high-risk individuals with be discussed along with the potential for contemporary population-based screening programmes to effect further reductions in breast cancer mortality. Notwithstanding issues of cost-efficacy, over-diagnosis is a concern for screening programmes with a dramatic rise in the number of cases of ductal carcinoma-in-situ (DCIS) diagnosed since the advent of breast cancer screening. Research is focussed on understanding the biology of DCIS and elucidating biomarkers reflecting propensity for either progression to invasive disease if untreated or risk of recurrence following breast conserving surgery for DCIS. Non-surgical methods for ablation of small primary breast cancers appear promising and results from novel cryotherapy are discussed. It is essential that patients receive adequate loco-regional treatments to prevent local recurrence and this applies both to surgery and radiotherapy. Newer techniques for delivering radiotherapy to the conserved breast have evolved rapidly in recent years with a growing interest in accelerated partial breast irradiation using methods such as intra-operative radiotherapy, partial breast irradiation and intensity-modulated radiotherapy. A dedicated section on radiation treatment will address omission of radiotherapy after wide local excision, accelerated partial breast irradiation and the controversial topic of regional nodal irradiation.

Several trials are investigating how resistance to anti-HER2 therapy can be overcome and why. anti-HER2 therapy which fails to completely block this signaling pathway in some HER2 positive tumors. Dual anti-HER2 therapy with trastuzumab and pertuzumab alongside chemotherapy may be appropriate as first line therapy for HER2 positive metastastic breast cancer. Similarly, there are ongoing efforts to elucidate the molecular underpinning of endocrine sensitive/resistant tumors. Selective estrogen receptor down-regulators (SERDs) have much potential for treatment of metastatic breast cancer and avoids some of the toxicities of chemotherapy.

There are no specific treatments for unselected triple negative breast cancer other than standard chemotherapy but BRCA1/2 mutation carriers may derive greater benefit from cisplatin. However, use of platinum salts for triple negative breast cancer (TNBC) cannot be recommended for inclusion in routine treatment schedules at the present time and usage should remain an individualized decision. Bisphosphonates have recently been incorporated into routine clinical practice for post-menopausal women with ER positive or ER negative tumors receiving chemotherapy. There is evidence from a meta-analysis that bisphosphonates reduce the rate of breast cancer recurrence (HR = 0.86) and mortality (HR = 0.82) for post-menopausal women (with no effect in pre-menopausal women). The prognostic value of tumor infiltrating lymphocytes (TiLs) is generating much interest and has been confirmed in a pooled analysis of 5 randomized controlled trials involving almost 1000 patients with early stage TNBC treated with anthracycline-based chemotherapy. TiLs are a surrogate for an adaptive immune response with both intra-tumoral and stromal TiLs adding significant information as a continuous variable to prognostic factors of age, tumor size and nodal status.

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