Estimating the Benefits of Therapy for Early-Stage Breast Cancer

The St. Gallen International Consensus Guidelines for the Primary Therapy of Early Breast Cancer 2019

H. J. Burstein; G. Curigliano; S. Loibl; P. Dubsky; M. Gnant; P. Poortmans; M. Colleoni; C. Denkert; M. Piccart-Gebhart; M. Regan; H.-J. Senn; E. P. Winer; B. Thurlimann

Disclosures

Ann Oncol. 2019;30(10):1541-1557. 

In This Article

Abstract and Introduction

Abstract

Background: The 16th St. Gallen International Breast Cancer Conference 2019 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer.

Design: Treatments were assessed in light of their intensity, duration and side-effects, estimating the magnitude of clinical benefit according to stage and biology of the disease. The Panel acknowledged that for many patients, the impact of adjuvant therapy or the adherence to specific guidelines may have modest impact on the risk of breast cancer recurrence or overall survival. For that reason, the Panel explicitly encouraged clinicians and patients to routinely discuss the magnitude of benefit for interventions as part of the development of the treatment plan.

Results: The guidelines focus on common ductal and lobular breast cancer histologies arising in generally healthy women. Special breast cancer histologies may need different considerations, as do individual patients with other substantial health considerations. The panelists' opinions reflect different interpretation of available data and expert opinion where is lack of evidence and sociocultural factors in their environment such as availability of and access to medical service, economic resources and reimbursement issues. Panelists encourage patient participation in well-designed clinical studies whenever available.

Conclusions: With these caveats in mind, the St. Gallen Consensus Conference seeks to provide guidance to clinicians on appropriate treatments for early-stage breast cancer and guidance for weighing the realistic tradeoffs between treatment and toxicity so that patients and clinical teams can make well-informed decisions on the basis of an honest reckoning of the magnitude of clinical benefit.

Introduction

The 16th St. Gallen International Breast Cancer Conference in 2019, held for the third time in Vienna, Austria, centered on individualized patient decision-making in early-stage breast cancer. A hallmark of the conference was the effort to base recommendations on the estimation of the magnitude of clinical benefit for specific treatments and interventions. This focus reflected several evolving factors in early-stage breast cancer, including a growing awareness of the importance of the long-term consequences of treatment on patient's well-being and function, the essential role of the patient in selecting optimal treatment options, the real-world estimate of benefit in terms readily understood by clinicians as well as patients, and a burgeoning set of treatment opportunities that may offer equal clinical benefit with less toxicity, or provide for a measurable improvement in outcomes. Decades of clinical trials have consistently demonstrated that most treatment interventions carry similar relative reductions in recurrence across the spectrum of risk defined by anatomical stage. The absolute benefits, however, are governed by the baseline risk of tumor recurrence. Recent experiences in countries with widespread screening programs for detecting early-stage breast cancer suggest steadily improving outcomes for most women with early-stage breast cancer. Indeed, the 'baseline' prognosis for many women with small, early-detected cancers receiving standard multi-disciplinary therapy has become so favorable that new, active treatments contribute only marginally to further reductions in the risk of recurrence and rarely affect overall survival. In addition, the appreciation of the biological heterogeneity of tumors continues to refine treatment algorithms in early-stage breast cancer. Treatment guidelines are no longer driven exclusively by the anatomic stage of the tumor or the histological subset of breast cancer. Decisions about optimal surgical, radiation therapy and medical approaches are increasingly tailored based on the initial response to neoadjuvant systemic therapy (NST). These developments demand that routine care be provided by an experienced multidisciplinary team of radiologists, surgeons, radiation oncologists, pathologists, and medical oncologists, and also demand engagement with the patient in a process of shared decision-making built on a realistic estimate of the magnitude of benefit for each component of therapy. In response to this progress, the 2019 St. Gallen Consensus Conference Guidelines offer important and exciting innovations, new from 2017, that are transforming care (Table 1).

The past 2 years have seen remarkable progress in our understanding of the biology and treatment of both late- and early-stage breast cancer (Table 2). The St. Gallen Consensus Guideline focuses on early-stage breast cancer, where as a consequence of multiple developments—improving overall prognosis, better tools for risk stratification, and care by integrated teams of providers—treatment recommendations are increasingly individualized. Systemic therapy substantially lowers the risk of local-regional tumor recurrence, which enables less surgery of the breast and axilla in many cases. Cancers believed highly sensitive to effective systemic therapy, such as HER2-positive tumors treated with anti-HER2 regimens, might warrant different approaches or durations of local-regional treatment than cancers not as responsive to systemic interventions. Clinicians increasingly interpret response to preoperative therapy in order to tailor surgical options and the need for post-operative treatment. New targeted therapies are emerging for biologically defined cancer subtypes. Sophisticated pathology and genomic signatures assays substantially refine the anticipated prognosis for long-term outcomes and thus inform treatment recommendations. However, therapies that carry robust impact on outcomes in high-risk tumors may translate into negligible returns, if any, for low-risk cancers. For some patients, there is a clear move to escalate therapy, such as longer durations of anti-estrogen treatment, more utilization of ovarian function suppression (OFS), treatment of residual tumor after NST, and dual targeting with anti-HER2 drugs. In other settings, there is a movement to de-escalate treatment, including the shortening or omission of adjuvant chemotherapy, the avoidance of axillary surgery, and shortened courses of radiation treatment.[58]

These advances pose challenges to consensus guidelines because it is more difficulty to confidently recommend treatments that apply to all patients, or even to all patients with a given stage or subset of breast cancer. They underscore the need for both clinicians and patients to explore the magnitude of benefit for a given treatment in the context of a particular cancer presentation. They invite opportunities for individual patients to articulate preferences regarding treatments that might afford narrow benefits, not affect overall survival, or carry substantial side-effects. Clinical trialists are also challenged to respond to these changes. There remains a vital need for improved treatment of patients at high risk of cancer recurrence, while for patients with low-risk tumors there are opportunities to explore which treatments might be judiciously, but safely, reduced or omitted. The former typically requires selection of high-risk tumors to create randomized trials of sufficient size to demonstrate activity; the latter often leads to single-arm studies that demonstrate adequate outcomes in cohorts which may be subject to biases of specific centers or clinical populations.

As a global consensus panel, the St. Gallen conference identified widespread variation in both patterns of care and access to treatment. Some of these disparities emerged when comparing less affluent societies against more affluent ones, and reflected profound differences in available resources for breast cancer screening, the availability of oncology services and specialty providers, and access to newer, more expensive diagnostics, treatments and supportive care. However, substantial differences in access to treatments exist among various developed countries, and many affluent countries have profound disparities between national health care systems and parallel, private systems, or based on socioeconomic and demographic factors. This heterogeneity in treatment styles and options was revealed through consensus discussions, and often affected the recommendations from panelists. Thus, while most recommendations reflect the broad majority of the Panel, few achieved fully uniform agreement, and many reflected the worldwide disparities in resources and access to integrated, multidisciplinary care and treatments.

The Panel acknowledged that for many patients, the impact of adjuvant therapy or the adherence to specific guidelines may have modest impact on the risk of breast cancer recurrence or overall survival. For that reason, the Panel explicitly encouraged clinicians and patients to discuss the magnitude of benefit for interventions routinely as part of the development of the treatment plan. The guidelines focus on common ductal and lobular breast cancer histologies arising in generally healthy women. Special breast cancer histologies may need different considerations, as do individual patients with other substantial health considerations. The panelists' opinions reflect different interpretation of available data and expert opinion where is lack of evidence and sociocultural factors in their environment such as availability of and access to medical service, economic resources and reimbursement issues. Panelists encourage patient participation in well-designed clinical studies whenever available. With these caveats in mind, the St. Gallen Consensus Conference seeks to provide guidance to clinicians on appropriate treatments for early-stage breast cancer and guidance for weighing the realistic tradeoffs between treatment and toxicity, so that patients and clinical teams can make well-informed decisions on the basis of an honest reckoning of the magnitude of clinical benefit.

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