Older women with estrogen receptor–positive breast cancer have poorer survival than younger women, but this gap might be closed by offering surgery to women over age 70 who are fit and have resectable tumors. According to a study presented at the 12th European Breast Cancer Conference (EBCC 12), which was held virtually this year, women over 70 who are fit can benefit from surgery, whereas their less fit, frailer counterparts can be treated with oral hormone therapy alone.¹

Data from the study were used to develop an online decision-making tool to evaluate whether older women with estrogen receptor–positive breast cancer would likely benefit from surgery. A second study suggested that this decision-support tool can influence management and help women learn about the risks vs benefits of treatment options.²

According to the lead author of both studies, Lynda Wyld, MD, Professor of Surgical Oncology at the University of Sheffield, United Kingdom, the majority of women over 70 can tolerate surgery, and all but the least fit should be offered this option.

Lynda Wyld, MD

Surgery vs Antiestrogen Tablets

The multicenter, prospective, observational study recruited 3,416 women from 56 cancer clinics in the United Kingdom over age 70 with operable breast cancer between 2013 and 2018.¹ Of these women, 2,979 with estrogen receptor–positive breast cancer were identified; 2,354 (82%) were treated with surgery and 500 (18%), with oral antiestrogen hormonal therapy alone.

“Women treated with oral antiestrogen tablets were about 8 years older and significantly less fit than those who got surgery,” Dr. Wyld explained.

The median age was 77 years among all patients, 76 years for patients who had surgery, and 84 years for those who had hormonal therapy alone. At baseline, patients who underwent surgery had fewer comorbidities and better performance of activities of daily living than those treated with hormonal therapy alone.

At a median follow-up of 52 months, an unadjusted analysis of overall survival revealed that 203 of 486 women (41.8%) in the hormone tablet–alone group died, compared with 336 of 2,307 women (14.6%) treated with surgery. Breast cancer–specific death rates were 113 of 2,293 (4.9%) in the surgery group and 45 of 476 (9.5%) in the tablet-alone group.

Adjusted Analysis

In an analysis adjusted for age, tumor stage, comorbidities, and levels of physical activity, 426 women in the surgery group and 240 women in the hormone tablet–alone group were identified who could be matched for age, fitness level, and frailty level. In the matched sample, death from any cause was reported in 25.6% of the surgery group and 34.5% for the tablet-alone group. Also in the matched sample, breast cancer–specific deaths were reported in 6.6% of women in the surgery group and 3.1% in the tablet-alone group.

No deaths were attributed to surgery among the larger group of 3,416 women. Only 2% of all 2,354 women treated with surgery had serious side effects attributed to surgery, including stroke or heart attack.

“For most women, surgery is well tolerated and should be the aim of treatment if possible, as we have shown that surgery is generally well tolerated and survival rates are slightly lower in women who do not have surgery,” said Dr. Wyld.

“However, when we looked at the two treatments in a less fit group of older women, these differences in breast cancer survival disappeared. In addition, their quality of life and their ability to engage in everyday activities deteriorated more after surgery than for women who just had hormone tablets. This also must be weighed against the potential difference in survival between surgery and primary hormone therapy [in estrogen receptor–positive breast cancer],” she said in a press release from the EBCC.

“These findings suggest that, for older, less fit, frailer women with [estrogen receptor–positive] breast cancer, hormone therapy alone is likely to be as good as surgery if their life expectancy is less than 4 to 5 years,” Dr. Wyld stated.

Need for Guidelines

“Until now, there have been no guidelines to aid in choosing the most appropriate treatment that takes into account fitness levels for women with estrogen receptor–positive breast cancer. We have used the data from this study to develop online tools to help determine whether older women will benefit from surgery or not, which may help in the decision-making process,” she explained. The link to the support tools is https://agegap.shef.ac.uk.

Preliminary results of a multicenter, cluster-randomized controlled trial of the Web-based decision-support tools developed by Dr. Wyld and co-investigators demonstrated the utility of these tools. One tool supports decisions about whether to have surgery plus adjuvant hormonal therapy or hormonal therapy alone. The second tool supports decisions about whether or not older women with breast cancer should have adjuvant chemotherapy after surgery. The tools included an online algorithm for clinicians and booklets for patients to read after their discussions with an oncologist.

The second study reported by Dr. Wyld included 1,339 women recruited from the first study.² All women were aged 70 or older and had operable estrogen receptor–positive breast cancer. A total of 46 breast cancer clinics participated and were randomly assigned to the decision-support tools (n = 21 clinics) or usual decision-making processes (n = 25 clinics). The aim of the study was to help support women in their choice of surgery or hormonal therapy alone, or chemotherapy or not after surgery.

“We found that treatment choices changed as a result of the decision-support tools, and patient knowledge about the available options was better. Patients rated the decision aids highly, and there was a small difference in subsequent quality of life among the women who were offered the choice between surgery or hormone-alone treatment,” she said.

Study Results

Interestingly, although the first study found that surgery was more effective in fit women with estrogen receptor–positive breast cancer, the second study found that the use of the decision-support tools led to more older women opting out of surgery.

In the clinics that used decision-support tools, more women had gained knowledge about the various treatment options—94% vs 74% of women in clinics randomly assigned to usual decision-making processes (P = .003)—and had greater awareness of treatment risks vs benefits (91% vs 79%, P = .054). Treatment choice was influenced as follows: 21% chose to have hormonal treatment as a result of using the decision-making tools, whereas 15% of those assigned to usual decision-making processes chose hormonal therapy alone (P = .02). The uptake of adjuvant chemotherapy was also lower among clinics randomly assigned to the decision-making tools: 10% vs 16% (P = .001).

“The use of older age–specific breast cancer decision-support tools increases knowledge of treatment options to facilitate shared decision-making. Their use alters treatment selection and enhances patient knowledge,” Dr. Wyld stated. Over the next 5 to 10 years, longer follow-up will look at whether the impact of deciding against surgery has had an impact on survival.

Comment on Study

Co-Chair of EBCC 12, Javier Cortes, MD, PhD, of the Institute of Breast Cancer, Barcelona, commented on these studies: “It can be hard to decide on the best treatment for older patients with breast cancer. When they are frail, unfit, and have several other health problems, quality of life may be more important to them than length of life. However, surgery is often the most effective primary treatment.”

Javier Cortes, MD, PhD

He continued: “The findings from these two linked studies will help patients and their doctors make their decisions based on the best available evidence, with the decision-support tools ensuring that the most appropriate treatment is chosen, based on the individual’s circumstances and wishes. It will be important to see what the longer follow-up reveals in terms of survival.” 

DISCLOSURE: Dr. Wyld reported no conflicts of interest. Dr. Cortes has received personal fees from Roche, Celgene, Cellestia, AstraZeneca, Biothera, Merus, Seattle ­Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp & Dohme, GlaxoSmithKline, Leuko, Novartis, Eisai, Pfizer, and Samsung Bioepis outside the submitted work; has received institutional research funding from Roche, Ariad, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffmann–La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur, Puma, Queen Mary University of London, and Seagen outside the submitted work; and has a patent issued for Medica Scientia Investigation Research.

REFERENCES

1. Wyld L, Reed M, Collins K, et al: Impacts of omission of breast cancer surgery in older women with ER+ early breast cancer. 12th European Breast Cancer Conference. Abstract 8A. Presented October 2, 2020.

2. Wyld L, Reed M, Collins K, et al: Cluster randomized trial to evaluate the clinical benefits of decision support interventions for older women with operable breast cancer. 12th European Breast Cancer Conference. Abstract 8B. Presented October 2, 2020.