Individualised assessment of initial response to therapy may pave the way for chemotherapy-sparing treatment, but it requires that multidisciplinary teams adapt their current practices
Personalised precision medicine doesn’t have to be expensive or complicated. For patients with early hormone receptor (HR)-positive and HER2-negative breast cancer, a key focus of our research in recent years has been individualising management by detecting early response to endocrine therapy to determine whether to de-escalate or escalate therapy. We have now established that giving patients a short period of endocrine therapy prior to surgery, then assessing the surgical specimen for response to endocrine therapy – with endocrine responsive tumours defined as those with ≤10% proliferation rate based on Ki67 measurements – enables us to decide whether chemotherapy is necessary. Five-year disease-free survival data from the WSG-ADAPT-HR+/HER2- trial indicate that adjuvant endocrine therapy alone is safe and effective in selected patients who might otherwise, using conventional clinicopathologic criteria, have also undergone chemotherapy (J Clin Oncol. 2022;40:2557–2567). Our group estimates that in Germany alone, we could omit 10,000–15,000 chemotherapy cycles per year using this procedure in routine clinical practice for patients with early breast cancer.
We also looked at the same concept of early response to endocrine therapy in HER2-positive disease in the WSG-ADAPT-TP trial, giving 12 weeks of therapy prior to surgery. Those patients who had a pathologic complete response at surgery were given low-level maintenance therapy for another year, with excellent outcomes after 5 years (J Clin Oncol. 2023;41:3796–3804). Similar results have been found in other studies, such as for patients with HER2-positive early breast cancer in the PHERGain trial in which imaging was used to assess response to targeted therapy, with the omission of chemotherapy in responders. Results at 3 years indicated no detriment to invasive disease-free survival in the approximately one-third of patients who responded to therapy prior to surgery and did not require subsequent chemotherapy (Lancet. 2024:S0140-6736(24)00054-0).
There are many aspects to personalising medicine, but early tumour response assessment is a highly effective and relatively inexpensive, patient-friendly concept, and lends itself well to being adopted in many countries, regardless of their economic capacity. Moreover, it offers the potential of customising precision medicine in many more patients than would molecular tests or costly assays, for example.
To implement tumour response assessment into clinical practice requires that we make changes to our usual processes. Traditionally, a patient would undergo surgery first and then receive endocrine therapy, whereas with this alternative strategy, a patient is first assessed and then sent home with a prescription of endocrine therapy for a month, after which they return for surgery. Although this change may seem unusual to some, we are already experiencing a similar adjustment to early breast cancer clinical practice in light of updated guidelines in the triple-negative and HER2-positive settings, where pre-operative chemotherapy is recommended for suitable patients (Ann Oncol. 2024;35:159–182). We may also need to change the mindset of those clinicians who think that such a relatively unsophisticated strategy is less important than a new complicated test: it has now been proven that a simple change to clinical practice – which might cost less – provides excellent clinical outcomes and is preferred by patients.
