Breast Cancer Recurrence Risk Varies by Molecular Subtype

Different molecular subtypes of breast cancer had varying rates and patterns of recurrence following surgery for early-stage disease, a large retrospective cohort study showed.

Overall, the 10-year freedom from ipsilateral, regional, and contralateral recurrence was 95.9%, 96.1%, and 96.5%, respectively. Using hormone receptor (HR)-positive (+)/HER2-negative (-) tumors as the reference, HR-/HER2+ breast cancer had the highest risk of ipsilateral recurrence and triple-negative breast cancer had the highest risk of regional and contralateral recurrence. Molecular subtype remained significantly associated with recurrence risk in proportional hazards regression analysis.

Patients 40 or younger had greater variation in recurrence patterns by subtype as compared with older patients, reported Han-Byoel Lee, MD, PhD, of Seoul National University College of Medicine in South Korea, and coauthors, in JAMA Surgery.

“Knowledge of the recurrence pattern may help identify periods of prevalent BC [breast cancer] recurrence and optimize the surveillance strategy,” the authors stated. “For example, physicians may consider surveillance every 6 months for patients with HR- subtypes, until 5 years after surgery, while surveillance for patients with HR+ tumors may continue to follow the current guideline of 1-year intervals. For younger individuals, more frequent surveillance may be recommended.”

Not only do the findings have implications for tailored screening intervals but for optimizing use of breast MRI, a focus of several recent studies, authors of an accompanying editorial noted.

“Breast MRI is known to be a useful adjunct in multiple aspects of breast cancer management,” wrote Anna Weiss, MD, of the University of Rochester in New York, and coauthors. “However, its exact role and indications are controversial, including for patients with a personal history of cancer…. The data currently available on breast MRI suggest that it may be beneficial in certain subsets of patients, including young patients and other high-risk populations, which is in line with the findings of [the Korean study]; however, these data must be interpreted cautiously because MRI has a significant false-positive rate.”

“[Lee and colleagues] demonstrated that women aged 40 years or younger with HR- breast cancer tended to have higher recurrence rates in the early postoperative periods,” continued Weiss and colleagues. “As such, young patients with HR-/ERBB2+ [HER2+] or triple-negative breast cancer may benefit from the addition of breast MRI as part of the surveillance in the first 2 to 3 years after surgery.”

Several studies have shown that the different molecular subtypes of breast cancer have different patterns of distant recurrence. However, few studies have examined the relationship between molecular subtype and locoregional recurrence, Lee and coauthors noted.

Investigators reviewed medical records of patients who had surgery for breast cancer at the Seoul National University College of Medicine from 2000 to 2018. Data analysis included 16,462 women who had a median age of 49 at the time of surgery. Women older than 40 accounted for 82.3% of the study population. The primary outcome was difference in patterns of annual incidence of ipsilateral, regional, and contralateral breast cancer recurrence.

The results showed that HR-/HER2+ tumors had almost a threefold higher rate of ipsilateral recurrence at 10 years as compared with HR+/HER2- tumors (HR 2.95, 95% CI 2.15-4.06). The risk of regional and contralateral recurrence was two to three times higher with triple-negative tumors (HR 2.95, 95% CI 2.37-3.67 and HR 2.12, 95% CI 1.64-2.75, respectively). After adjustment for clinicopathologic variables that influence recurrence, older patients had a lower risk of ipsilateral and contralateral recurrence.

With regard to patterns of recurrence, ipsilateral recurrence exhibited a double peak, the first occurring at year 2 and the second from years 8 to 9. Both HR-/HER2+ and triple-negative tumors exhibited the double-peak patterns of recurrence, but the recurrence incidence was higher for HR+/HER2- tumors. HR+/HER2- tumors exhibited a steady increase in recurrence with no distinguishable peaks, the authors reported.

Patients with triple-negative breast cancer had the highest risk of regional recurrence, which reached a peak at 1 year and persisted to 2 years. Thereafter, the incidence gradually decreased except for the HR+/HER2- subtype, which had a stable and increasing pattern of annual incidence. Annual rate of contralateral recurrence increased for all subtypes, but was highest for triple-negative tumors over 10 years.

Analysis of recurrence patterns by age showed that the differences noted for the molecular subtypes were greater among younger women. The double peaks associated with ipsilateral recurrence were more prominent in younger patients. The incidence of regional recurrence decreased during the first 5 years except for triple-negative tumors, which exhibited a rebound thereafter. Annual incidence of contralateral recurrence was higher with more diverse patterns among younger patients.

“Validating our study at a multi-institutional level with a large number of patients, taking into account the recent advances in BC treatments, would be necessary to generalize our findings,” the authors concluded.

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