Surgery Boosts Survival in Older Breast Cancer Patients

SAN ANTONIO — A comprehensive patient-level meta-analysis of three randomized trials demonstrated that compared with surgery deferral, immediate breast surgery significantly reduces both local progression and long-term mortality in women aged 70 years or older with operable breast cancer.

The findings, presented at the San Antonio Breast Cancer Symposium (SABCS) 2024, challenge the practice of offering endocrine therapy alone to older patients and underscore the importance of immediate surgical intervention.

“Despite guidelines, as women get older, the rates of surgery tend to decrease, especially in women who are older than 80 years,” said Robert Hills, professor of medical statistics at the University of Oxford, Oxford, England, during his presentation. This practice pattern, documented by the National Audit of Breast Cancer in Older Patients, prompted researchers to investigate whether immediate surgery improves outcomes in older women compared with delaying surgery until local progression occurs.

Methodology

The meta-analysis included 1082 women aged 70 years or older from three randomized trials initiated in the 1980s. The median age at randomization was 76 years (interquartile range, 73-80 years), and 63% of the participants had tumors > 20 mm in diameter. All patients received tamoxifen for at least 5 years, and none of the trials included scheduled radiotherapy or chemotherapy.

Monica Morrow, MD, clarified that this conservative approach of offering endocrine therapy alone has specific applications: “The way these trials have been applied is using endocrine therapy as an alternative to surgery in older women with other illnesses, which rendered them high risk for serious complications in the operating room or who were at high risk of dying of something other than breast cancer. This was not an approach routinely offered to healthy older women in the US.” Morrow, chief of Breast Surgery at Memorial Sloan Kettering Cancer Center, New York City, was not involved in the study.

Immediate Surgery Reduces Locoregional Failure Risk

The results showed a highly significant reduction in locoregional failure with immediate surgery (relative risk [RR], 0.24; 95% CI, 0.19-0.30; P 

In an interview, Morrow noted that this information is particularly valuable in patient discussions: “It is useful in helping to convince patients who are reluctant to have surgery but are good candidates for surgery that there are benefits to them other than living longer since some older patients say they value quality of life over length of life, and local control improves quality.”

The study also revealed significant improvements in distant recurrence (RR, 0.72; P = .003), breast cancer mortality (RR, 0.68; P = .002), and all-cause mortality (RR, 0.83; P = .016). However, these survival benefits only emerged after the first year of follow-up.

“What is important is the fact that there is little effect on distant recurrence or breast cancer mortality early on in the follow-up period,” Hills explained during his presentation. “The benefit of immediate surgery on distant recurrence and mortality only occurs later on and with longer follow-up.”

Surgical Approaches and Long-Term Outcomes

Among the 518 women allocated to immediate surgery, 45.7% underwent mastectomy, 47.3% underwent breast-conserving surgery, and 7.0% received neither. In the deferred surgery group, approximately 60% of patients never required surgery because of the absence of local progression, as Hills noted during the discussion after the presentation.

He also emphasized the temporal pattern of benefits from immediate surgery. The distant recurrence rate ratio showed a progressive improvement over time: 0.97 during years 0-1, 0.73 during years 2-4, and 0.52 after year 5. This trend in progressive risk reduction was statistically significant (P = .012). According to Hills, this pattern suggests that “the full benefit of immediate surgery may take several years to manifest.”

Morrow provided her perspectives on these findings: “Studies in early-stage breast cancer looking at the survival benefit of adding radiation to surgery show that the survival benefit does not become evident for 15 years. If the tumor has not spread at diagnosis, it needs time to grow and spread, so the mortality impact of not treating the primary tumor optimally takes time to happen.”

Implications for Clinical Practice and Future Trials

When asked about the implications of the study for modern practice, Hills emphasized the methodological significance of these findings.

Even with such a dramatic difference in intervention (surgery vs no surgery), the survival benefits were delayed and modest (smaller than the local control benefits) and, therefore, required longer follow-up to become apparent, Hills said. “This is important because it shows that trials may need to be larger and be followed up for longer in order to yield reliable results on breast cancer mortality.”

He further elaborated on the study’s robust methodology. “Our approach has always been to collaborate with the individual trialists who agree to share with us updated data on every single woman in their trials without fee,” Hills explained in the interview. “We have a standard data template into which all our data are put after checking. The advantage of this is that we are very confident of data quality, and all the definitions are harmonized.”

In an interview, Morrow emphasized that surgery has long been a safe option for most older patients: “The 30-day operative mortality for breast surgery in older women is

She also noted that for patients who cannot have surgery, cryoablation is another technique that was not available in the past, which can maintain local control.

The findings also have implications for treatment de-escalation strategies, an area where significant progress has already been made, according to Morrow.

“De-escalation has already been investigated in women > 70 with hormone receptor–positive HER2-negative cancers,” she explained. “Sentinel node biopsy is no longer recommended for these tumors; many women can avoid radiotherapy entirely, and for those who cannot, partial breast irradiation or hypofractionated whole breast radiotherapy are well-tolerated options.”

She added, however, that de-escalation of systemic therapy in this group remains a challenge not yet fully addressed.

“For women with triple-negative or HER2-positive breast cancers, we still stage nodes, and it is worth considering when that is not necessary for systemic therapy decisions in women in their 80s and older.”

Future Directions

According to Hills, although the trials were conducted in the 1980s, the findings remain relevant today. He added that these results could inform the planning and interpretation of trials investigating less extreme de-escalation of surgery or radiotherapy.

“The forthcoming update of the NSABP B-06 trial comparing mastectomy versus lumpectomy is expected to provide additional insights,” Hills said in an interview.

He noted, however, that the historical context may affect the interpretation of the results. As Hills pointed out during the discussion session, “What was considered older 40 years ago is different from what we would think about what an older woman is today. Things have changed from that point of view.”

In the interview, Hills emphasized that age alone should not be the determining factor in surgical decisions for elderly breast cancer patients, according to the findings of this study.

“There is no evidence of excess mortality from causes other than breast cancer, and the benefits were consistent across all patient subtypes,” he said. “The absence of excess mortality from causes other than breast cancer, combined with the consistent benefits across patient subtypes, supports the consideration of immediate surgery in healthy older women with operable breast cancer.”

As Hills concluded, these results provide evidence that immediate surgery should be strongly considered for older women with operable breast cancer, particularly given the significant long-term survival benefits and the absence of increased non-breast cancer mortality. He added, however, that individual treatment decisions should still account for patient-specific factors and preferences.

Morrow echoed the importance of individualized treatment decisions. “Health status, rather than chronologic age, should be the determinant of whether or not surgery is the initial step in treatment. Surgery remains the best approach for women in their 70s and 80s who are in good health. It provides local control and appears to have a survival benefit. For those not in good health, endocrine therapy with surgery reserved for those with disease progression is a nice alternative.”

The study was funded by Cancer Research UK and the Medical Research Council. Hills and Morrow reported no relevant financial relationships.

Christos Evangelou, PhD, is a freelance medical writer and science communications consultant.