Non-frail patients with early-stage breast cancer have an increased risk of worsening frailty status after locoregional therapy, according to research published in JAMA Surgery

The study showed an increased risk of worsening frailty status among patients who were deemed robust at baseline, compared with patients who were already frail at baseline. The data also showed an increased risk of worsening frailty status among Black patients, those who were 75 years of age or older, and patients who underwent mastectomy.

The study included 31,084 women with ductal carcinoma in situ or stage I hormone receptor-positive, HER2-positive breast cancer. The patients were 65 years of age or older, with a median age of 73 years.

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The patients received locoregional therapy between January 2010 and October 2015. Most patients (77.4%) underwent lumpectomy — alone (14.1%), in combination with radiotherapy (RT; 13.3%), in combination with axillary surgery (12.6%), or in combination with axillary surgery and RT (37.4%). 

Among the patients who underwent mastectomy (22.6% overall), 2.7% underwent mastectomy alone, and 19.9% underwent mastectomy and axillary surgery.

At diagnosis, 55.6% of patients were deemed robust, 40.3% were prefrail, 3.8% had mild frailty, and 0.3% had moderate to severe frailty. After treatment, 21.4% of patients experienced worsening frailty.

An adjusted analysis revealed higher odds of worsening frailty status among patients who:

  • Were deemed robust vs frail at baseline (odds ratio [OR], 6.12; 95% CI, 2.80-13.35)
  • Underwent mastectomy vs lumpectomy (OR, 1.31; 95% CI, 1.23-1.39)
  • Were Black vs non-Hispanic White (OR, 1.12; 95%CI, 1.01-1.24).

“That women in the robust category were more likely to develop frailty after locoregional therapy suggests that thoughtful treatment decisions should be undertaken in all older women, not simply those who have frailty at diagnosis,” the researchers wrote. 

“Tailoring locoregional therapy intensity in this population is important as clinical trial data have shown equivalent survival between lumpectomy and mastectomy and that RT and axillary surgery can be safely omitted in older adults with early-stage HR-positive disease,” they noted.

The researchers also found that increasing age was associated with a progressively higher risk of worsening frailty status. Compared with patients aged 65-69 years, the ORs for worsening frailty status were 1.21 (95% CI, 1.12-1.31) for patients aged 75-79 years, 1.53 (95% CI, 1.40-1.66) for patients aged 80-84 years, and 1.94 (95% CI, 1.75-2.13) for patients 85 and older.

“Given the substantial proportion of women experiencing worsening frailty and the significant difference by breast surgery type, frailty status as a cancer therapy outcome should be further explored,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Minami CA, Jin G, Freedman RA, Schonberg MA, King TA, Mittendorf, EA. Association of surgery with frailty status in older women with early-stage breast cancer. JAMA Surg.  Published online March 15, 2023. doi:10.1001/jamasurg.2022.8146