Mini Oral – BC, early stage

In this video, Dr Eline Naert, medical oncologist at the University hospital Ghent discusses a selection of abstracts that were presented during the mini oral session on early-stage breast cancer at ESMO 2024.

In a first of two abstracts discussing early-stage triple negative breast cancer (TNBC), data from the Netherlands cancer registry were used to evaluate whether pathological complete response (pCR) rate is also associated with overall survival (OS) in stage I TNBC patients treated with neoadjuvant chemotherapy.1 A total of 1,144 patients treated with anthracycline and taxane-based neoadjuvant chemotherapy were included in the analysis, of whom 472 (41.3%) received a platinum-based regimen and 282 (24.7%) received adjuvant capecitabine. The pCR rate after neoadjuvant chemotherapy was reported at 57.3%, with younger age and a grade 3 tumour being factors that increased the likelihood for a pCR. In contrast, the pCR rate was lower among patients with lobular disease. Importantly, the study confirmed the surrogacy of pCR for OS, with a 4-year OS rate of 98% and 93% for patients with and without a pCR, respectively (HR[95%CI]: 0,29[0.15-0.56]).1

In the French, retrospective PROMENADE study (N=114), the investigators evaluated the efficacy of the KEYNOTE-522 regimen in patients with ER-low (1-9%) breast cancer.2 This regimen has become the standard of care for patients with early-stage TNBC but given the fact that ER-low patients were excluded from this study, it is unclear how the combination of neoadjuvant chemotherapy and pembrolizumab performs in these patients. The analysis mainly included patients with a tumour size ≥T2 (89%) and a tumour grade of 3 (86%), with 49% having nodal involvement. The pCR rate in this patient population was reported at 75%, which is better than what was seen in KEYNOTE-522 (64%) and KEYNOTE-756 (24%), which evaluated a similar regimen in ER-positive patients. As such, these findings provide support for the use of the KEYNOTE-522 regimen in patients with ER-low, HER2-negtaive early breast cancer.2

In addition to this, Dr Naert selected three abstracts in patients with early-stage hormone-receptor (HR)-positive breast cancer. The phase III NATALEE study previously showed a statistically significant benefit in invasive disease–free survival (iDFS) with the addition of ribociclib to adjuvant therapy with a non-steroidal aromatase inhibitor (NSAI) in patients with early-stage HR-positive breast cancer. During ESMO 2024, a subgroup analysis of this study was presented focusing on younger patients (< 40 years), a subgroup of patients who historically present with a more aggressive disease. The addition of ribociclib also proved to induce a significant benefit in these younger patients, with an absolute difference in iDFS of 5.1% at 3 years (90.1% vs. 85.0%; HR[95%CI]: 0.546[0.321-0.929]). Apart from a higher incidence of neutropenia and hot flushes, there were no major differences in adverse events with the NATALEE regimen in patients <40 and ≥40 years old.3 As such, these findings show that the addition of ribociclib to a NSAI provides consistent benefit to patients with HR-positive early breast cancer, irrespective of age.

The second presentation on early-stage HR+ breast cancer also focused on younger patients. Younger age has historically been associated with an increased risk of recurrence and a lack of treatment adherence has been hypothesized as one of the reasons for this. To address this issue, the presented study used data from the French National Health Data System to estimate the potential gains in DFS that may be achievable by improving endocrine therapy (ET) persistence.4 The analysis confirmed that younger age was indeed associated with a decreased DFS in patients with HR-positive disease, but this was the case in HR-negative patients. In addition, younger age proved to be associated with a lower persistence to ET. Interestingly, in patients younger than 34 years old, strict ET persistence was shown to increase the 5-year DFS rate from 75.8% to 81.4%, corresponding to an absolute benefit of 5.6%.4 As such, these data underscore the need for tailored strategies to improve ET persistence in (very) young patients with HR-positive early breast cancer.

A final study used data from the HERA study to gather information on the optimal antihormonal therapy for premenopausal women with HR-positive, HER2-positive early breast cancer. The analysis included a total of 965 patients and showed that the use of ovarian function suppression (OFS) was independently associated with an improved prognosis, regardless of whether the patient received chemotherapy with or without trastuzumab. With respect to the choice of ET, the data showed a better DFS and OS when OFS was combined with an aromatase inhibitor compared to tamoxifen.5 As such, these findings illustrate the importance of optimizing the ET in patients with HR-positive, HER2-positive early breast cancer.