Primary medical therapy and breast conservation treatment: the medical oncology perspective

Primary systemic therapy (PST) is a widely adopted strategy for increasing operability and breast conservation rates. Although first generation PST trials failed to demonstrate improvements in disease free and overall survival compared to adjuvant systemic therapy (AST), they did demonstrate a strong association between attainment of pathologic complete response (pCR) and improved survival outcomes, leading to the widespread adoption of pCR as the primary endpoint in subsequent PST trials. First generation trials also showed that preoperative PST can improve breast conservation rates and downstage the axilla. Although individual trials did not demonstrate statistically significant increase in local recurrence with PST when compared to AST, a recent meta-analysis did note an increased in such risk, mainly driven by trials in which surgery was omitted in patients with good response to PST. Successive generations of PST clinical trials have since explored the activity of taxanes, optimization of anthracycline and taxane dose and schedules, incorporation of single and dual anti-HER2 therapy in HER2 overexpressing breast cancer, the use of platinums in triple negative breast cancer, and the role of endocrine therapy in hormone receptor positive breast cancer. While these PST trials have generally found increased pCR rates with the introduction of modern chemotherapy regimens and targeted therapies, they have not consistently demonstrated further improvements in breast conservation rates compared to first generation regimens. The reasons for this are complex and may lie beyond differences in anti-tumour activity between different systemic regimens but rather in other potential confounding factors such as tumour to breast volume ratio, tumour location, multicentricity as well as patient or surgeon preference.