Managing Unseen Risks: Understanding Recurrence in Early Breast Cancer With No or Limited Nodal Involvement

With support from Novartis, OncLive sat down with Erika Hamilton, M.D., medical oncologist and the Director of Breast Cancer Research at Sarah Cannon Research Institute to discuss the risk of recurrence in patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer (eBC), regardless of nodal involvement.

For patients who have experienced HR+/HER2- eBC, the risk of recurrence remains a persistent and significant concern. Despite the curative intent of early-stage treatment, including adjuvant endocrine therapy (ET), many patients — particularly those with stage II or III tumors, regardless of nodal involvement — face a significant risk of their cancer returning.1,2

“Though an initial cancer treatment may be successful, once someone has had an invasive cancer there’s always a chance the cancer could return,” said Dr. Hamilton.

Although traditionally viewed as lower-risk, patients with limited nodal involvement (1-3 positive nodes, N1) or no nodal involvement (no positive nodes, N0) can still face a risk of recurrence.1,3-5

Given that most recurrences present as metastatic disease, understanding which of these patients are most at risk and partnering with them to address it is of critical importance to help patients remain cancer-free.1-3

What Drives High Risk of Recurrence in Patients With Limited Nodal Involvement?

“Unfortunately, I’ve seen plenty of patients who did not have lymph node involvement but had other high-risk factors who ultimately experienced cancer recurrence,” said Dr. Hamilton.

Routine screenings play a crucial role in identifying tumors at early stages, enabling timely and effective intervention. Sometimes, this means finding tumors with high-risk characteristics before they have compromised the lymph nodes. With this in mind, evaluating recurrence risk is critical to determine an optimal approach to adjuvant therapy, but doing so can be complex and requires consideration of many individualized biological and anatomical factors. Histologic grade, ER- vs. PR-positive receptor status, and factors like tumor size, circulating and disseminated tumor cells, Ki-67 proliferation index, age, menopausal status, and comorbidities, can help clinicians develop a more precise and personalized evaluation of recurrence risk, allowing for tailored treatment strategies that align with the patient’s unique profile.

“Even for these patients who have limited or no nodal involvement, we must take into account these several important factors when evaluating their risk of recurrence to make the most well- informed treatment recommendations that we can,” stressed Dr. Hamilton.

Discussing the Need for Adjuvant Therapy With Eligible Patients

“Evaluating this risk is only one piece of the puzzle,” added Dr. Hamilton. “As health care providers, we need to also ensure that our patients fully understand their risk of recurrence (both short term and long term) and, for those who qualify, how adjuvant therapy may help reduce it.”

An adjuvant therapy regimen is vital for helping reduce the risk of recurrence in patients with HR+/HER2- eBC, including those with N1 and high-risk N0 disease. However, the physical and emotional tolls of initial treatment may make the idea of starting a new therapy overwhelming for patients. While many patients struggle with post-traumatic stress disorder, or PTSD and remain hypervigilant of any symptom that could mean their cancer is back, some patients in remission are often eager to move past their cancer diagnoses and may be resistant to adjuvant therapy, holding on to the belief that, if caught and treated early, they won’t ever see cancer come back.

“Honest and direct communication with patients will help increase their level of understanding on their risk and the potential benefits of different adjuvant therapies. This understanding helps them make choices about which therapy to initiate and can also help with adherence,” explained Dr. Hamilton. “Additionally, concepts like absolute and relative risk reduction can be confusing for patients. While absolute risk reduction gives a sense of how much a treatment will reduce one’s risk of recurrence, it doesn’t offer context relative to baseline risk. On the other hand, relative risk reduction captures this important context but doesn’t give a sense of effect size.”

Additionally, knowing that more than half of recurrences of breast cancer occur after the first five years, the nuances of these metrics become even more important.6 It is paramount that physicians take time upon completion of an initial treatment regimen to support patients with clear and straightforward explanations so they can make the most informed decisions possible.

“As health care providers, we share the same ultimate goal as our patients: to put their cancer in the rearview mirror,” said Dr. Hamilton. “As the adjuvant therapy landscape evolves, being open and transparent in discussions with our patients is paramount to working with them on making the most informed choices they can regarding adjuvant therapy in order to reduce the chance of recurrence. Whether it’s using visuals to convey the statistics or revisiting my recommendation at a subsequent appointment after they’ve had time to digest our initial conversation, I always do everything I can to make sure they understand their risks and the treatment options available to them.”

To learn more about managing the risk of recurrence for eBC patients, visit eBCRisk.com.

References:

1. Pan H, Gray R, Braybrooke J, et al; EBCTCG. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846. doi:10.1056/NEJMoa1701830
2. Pan H, Gray R, Braybrooke J, et al; EBCTCG. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846;(suppl). doi:10.1056/NEJMoa1701830
3. Gomis R, Gawrzak S. Tumor cell dormancy. Mol Oncol. 2017;11(1):62-78. doi: 10.1016/j.molonc.2016.09.009.
4. Curigliano G, Ciruelos E, Kalinsky K, et al. Short-term risk of recurrence in patients (pts) with HR+/HER2− early breast cancer (EBC) treated with endocrine therapy (ET) in randomized clinical trials (RCTs): A meta-analysis. Presented at the American Society of Clinical Oncology Annual Meeting; May 29, 2024; Chicago, USA.
5. Slamon D et al. Rationale and trial design of NATALEE: a Phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2- early breast cancer. Ther Adv Med Oncol. 2023;15:17588359231178125. doi: 10.1177/17588359231178125
6. Wangchinda P, Ithimakin S. Factors that predict recurrence later than 5 years after initial treatment in operable breast cancer. World J Surg Oncol. 2016;14(1):223. doi: 10.1186/s12957-016-0988-0