The 46th San Antonio Breast Cancer Symposium (SABCS 2023) was held in San Antonio, Texas, where numerous significant studies were presented. Oncology Frontier had the privilege of inviting Professor Jiayi Chen from the Department of Radiation Oncology at Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, to share the latest developments in the field of breast cancer radiotherapy presented at this SABCS conference.Professor Jiayi Chen: At this SABCS conference, several studies on radiotherapy impressed me, and I will introduce them to you next.
GS02-02: Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study
Patients with positive sentinel lymph nodes (SLN) after neoadjuvant chemotherapy (NAC) have a higher risk of residual lymph node burden, and axillary lymph node dissection (ALND) is currently considered standard treatment. About 1.5% of patients receiving NAC have residual isolated tumor cells (ITCs), and data on the likelihood of finding additional positive lymph nodes in these patients are scarce, making the benefits of ALND unclear. Thus, the approach to axillary surgery in these patients is not standardized.
The OPBC05/EUBREAST-14R/ICARO study (hereinafter referred to as EUBREAST-14R) is a European multicenter retrospective study. It aims to assess the frequency of finding additional positive lymph nodes, identify factors associated with ALND, and compare the tumor prognosis between patients who undergo ALND and those who do not after residual ITCs are found in SLNs. Researchers collected data from 42 centers, including 20 from the Oncoplastic Breast Consortium (OPBC) and the European Breast Reconstruction Alliance (EUBREAST) networks, and 22 from North and South America. The study included patients diagnosed with cT1-4N0-3 breast cancer, who underwent axillary staging with SLN biopsy (SLNB) or targeted axillary dissection (TAD) after NAC to identify breast cancer patients with residual ITCs [ypN0(i+)]. Single-tracer mapping was allowed for cN0 patients, while cN+ patients required dual-tracer mapping or TAD. Axillary treatment included completing ALND and/or lymph node radiotherapy (RT). Competing risk analysis was conducted to assess the cumulative incidence of axillary recurrence (AR), locoregional recurrence (LRR), and any invasive (local or distant) recurrence. Researchers compared the 5-year cumulative incidence rates of patients who underwent ALND with those who did not using Gray’s test.
The results of the EUBREAST-14R study indicate that patients with low residual burden in SLNs after NAC can be exempted from ALND without affecting the safety of anticancer treatment, as there was no significant difference in the 5-year axillary recurrence rate (4.6% vs 4.1%, P=0.8). It’s worth mentioning that the European region is more proactive regarding regional lymph node radiotherapy, hence over 80% of the patients in this study received it. Under this premise, the researchers further hypothesized whether it’s possible to selectively exempt patients from radiotherapy on the basis of being exempted from ALND, aiming for a more thorough de-escalation of treatment for patients. We await the results with great interest.
GS02-05：Overview of Axillary Treatment in Early Breast Cancer: patient-level meta-analysis of long-term outcomes among 20,273 women in 29 randomised trials
At this SABCS conference, an update was also presented on the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview of 29 randomized trials concerning axillary treatment in early breast cancer (GS02-05). The study encompasses two main aspects, the first of which is the extent of ALND surgery, divided into two eras: the pre-sentinel era (no axillary surgery vs. ALND) and the sentinel era (SLNB vs. ALND).
The second aspect compares the efficacy of ALND with axillary lymph node radiotherapy, also divided into the pre-sentinel era and the sentinel era. The results indicate that, regardless of the era, the extent of ALND surgery does not impact the safety of anticancer treatment, and ALND and axillary lymph node radiotherapy are equivalent in terms of their effectiveness in anticancer treatment.
Interestingly, compared to ALND, radiotherapy to the axillary lymph nodes can reduce the incidence of upper limb lymphedema by about 20%. In China, many single-center or multi-center studies have used the status of the SLN to construct nomograms and predict the involvement rate of non-sentinel lymph nodes, thereby deciding whether to perform radiotherapy. Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, has conducted a similar study, obtaining results akin to those in the EBCTCG overview, namely that axillary lymph node radiotherapy, compared to ALND, can reduce the occurrence rate of upper limb lymphedema by about 20%. However, there are still unresolved issues. As surgery accumulates more evidence supporting the exemption of ALND, what strategy should radiation therapy adopt to follow the surgical de-escalation treatment? Should it, like the EUBREAST-14R study, predominantly replace ALND with a high proportion of axillary lymph node radiotherapy, or should patients be more finely stratified to decide whether a comprehensive de-escalation of axillary local treatment is possible? This question requires further exploration by radiation oncologists and surgeons together.
GS02-07：Loco-regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304
At this SABCS conference, the NRG Oncology/NSABP B-51/RTOG 1304 trial (hereinafter referred to as NSABP B-51) first announced its follow-up results, delving into whether axillary de-escalation treatment is feasible for the patient group diagnosed preoperatively with positive axillary lymph nodes, which became pathologically negative after neoadjuvant treatment.
Currently, patients without NAC and those with cN0 or low-burden positive sentinel lymph nodes can be exempted from axillary lymph node dissection (ALND). This decision is supported by a series of clinical studies, including the Z0011 and AMAROS studies, and guidelines recommend exempting ALND for patients with cN0 and 1 to 2 positive lymph nodes (LNs). So, for patients whose ALN status is downgraded after NAC, is it possible to exempt them from radiotherapy when exempting ALND?
The NSABP B-51 trial enrolled patients with cT1-3N1M0 before NAC, who were deemed ypN0 after sentinel lymph node biopsy (SLNB) or ALND post-NAC, and randomly assigned them to groups. If breast-conserving treatment was used, they were randomly assigned to the whole breast irradiation group or the whole breast + regional nodal irradiation (RNI) group; if the patient underwent mastectomy, they were randomly divided into the post-mastectomy radiotherapy (PMRT) + RNI group and the no postoperative radiotherapy group. The primary endpoint of the NSABP B-51 trial was invasive breast cancer recurrence-free interval (IBC-RFI), with secondary endpoints including locoregional recurrence-free interval (LRRFI), distant recurrence-free interval (DRFI), disease-free survival (DFS), and overall survival (OS).
The results showed that, in this study, there was no significant difference between the two groups in terms of invasive breast cancer recurrence-free interval (IBC-RFI), distant recurrence-free interval (DRFI), disease-free survival (DFS), and overall survival (OS).
In this study, ypN0 status was evaluated through two methods: SLNB and ALND. It’s important to note that SLNB in these patients could have at least a 10% false-negative rate. Even so, we can conclude that patients with cN1, who achieve ypN0 status after NAC, have a lighter tumor burden and the possibility of reducing treatment in the axilla. Additionally, in the mastectomy subgroup, the addition of radiotherapy showed a trend toward reducing local recurrence, though not statistically significant. Another subgroup I’m particularly interested in is those who underwent mastectomy and SLNB but not ALND, to see if there’s a difference in regional recurrence with or without RNI. However, the conference did not release related study results, and I look forward to the full text publication to get information on these patients.
GS02-08: Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients aged 50-69 with genomically-selected favorable Stage I breast cancer
Several randomized trials have shown that radiotherapy after breast-conserving surgery (BCS) significantly improves local control of invasive breast cancer. However, not all subgroups gain the same absolute benefit from radiotherapy, with survival benefits seeming limited to those subgroups where radiotherapy substantially reduces the risk of recurrence. The IDEA trial explored the possibility of exempting low-risk, breast-conserving populations from radiotherapy. The study enrolled postmenopausal breast cancer patients aged between 50 and 69, with an Oncotype DX recurrence risk score of ≤18, who agreed to undergo at least 5 years of endocrine therapy (ET) and research monitoring. The primary endpoint was the recurrence rate of breast cancer patients during a 5-year follow-up period after breast-conserving surgery.
Multiple randomized trials have shown that radiotherapy after breast-conserving surgery (BCS) significantly improves local control of invasive breast cancer. However, not all subgroups achieve the same absolute benefit from radiotherapy, with survival benefits seemingly limited to those subgroups where radiotherapy significantly reduces the risk of recurrence. The IDEA trial explored the question of whether radiotherapy can be omitted for the low-risk breast-conserving population. This study enrolled postmenopausal breast cancer patients aged 50 to 69, with an Oncotype DX recurrence risk score ≤ 18, who agreed to undergo at least 5 years of endocrine therapy (ET) and research monitoring. The primary endpoint was the rate of recurrence during the 5-year follow-up period after breast-conserving surgery.
From June 2015 to October 2018, 200 eligible patients from 13 U.S. institutions were enrolled. The median follow-up time was 5.2 years, with clinical follow-up of at least 56 months for 186 patients. Both overall and breast cancer-specific 5-year survival rates were 100%, and the 5-year recurrence-free rate was 99%. The crude incidence rates of ipsilateral breast events (IBE) during the entire follow-up period were 3.3% (2/60) for patients aged 50–59 and 3.6% (5/140) for those aged 60–69; the crude recurrence rates were 5.0% (3/60) for patients aged 50–59 and 3.6% (5/140) for those aged 60–69.
Although it was a single-arm study, the results indicate that patients who underwent breast-conserving surgery without radiotherapy had a 5-year recurrence rate of ≤5%. The researchers interpreted these results with great caution, stating that the recurrence rate of less than 5% preliminarily meets the primary endpoint designed by the researchers. However, whether this rate is satisfactory requires long-term consideration. The researchers also emphasized multiple times in the discussion that during the entire study process, the decision to exempt radiotherapy for postmenopausal elderly patients may lead some patients to experience anxiety about recurrence, while increasing reliance on endocrine therapy, which often has more significant side effects for older patients. Therefore, the choice of treatment needs more comprehensive discussion.
Personally, I believe that de-escalating treatment for a subset of low-risk patients is feasible. However, how to balance local and systemic treatments and how to achieve the highest overall treatment acceptance for patients undergoing de-escalation is a topic worth discussing.
Furthermore, in recent years, we have been discussing short-course radiotherapy and even a single preoperative high-dose radiotherapy. Preoperative radiotherapy has two advantages: first, the surgical treatment after radiotherapy can completely remove the tumor in the irradiated area, reducing our concerns about fibrosis caused by a single high-dose radiotherapy, resulting in better cosmetic outcomes; second, a single preoperative high-dose radiotherapy allows us to observe the tumor’s response, offering patients a chance for pathological complete response (pCR). From this single-arm study, we can observe two patterns: first, the higher the single dose, the higher the pCR rate; second, the longer the interval between radiotherapy and surgery, the higher the pCR rate. These data provide us with great confidence in treatment. If we can move radiotherapy from postoperative to preoperative and achieve short-course treatment, patients will have a better treatment experience, less concern about breast-conserving therapy, and significantly reduced dependence on and psychological burden of endocrine therapy.
Summary
In summary, the progress in the field of radiotherapy at this SABCS: including escalation and de-escalation. We can exempt a part of extremely low-risk patients from radiotherapy or significantly shorten the course of radiotherapy to achieve de-escalation treatment through precision medicine. When surgery has sufficient evidence to support the exemption of ALND for patients with low SLN burden, current evidence shows that most patients can achieve a comprehensive de-escalation of local axillary treatment, though some may still require additive radiotherapy for regional treatment. For radiation oncologists, communicating with doctors from other departments and providing precise treatment to patients both technically and strategically is crucial.
Professor Jiayi Chen
Director of the Department of Radiation Oncology at Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine
#Interview#Commentary#SABCS 2023#Breast Cancer
