Surgery or Endocrine Therapy Alone? What Does the Evidence Say for Breast Cancer in Older Age?
In this article
Surgery or Endocrine Therapy Alone? What Does the Evidence Say for Breast Cancer in Older Age?
Breast cancer is being diagnosed at ever older ages, and the best treatment for women over 80 is a frequent question. In hormone receptor-positive tumors, treatment with hormone-suppressing drugs alone, without surgery (primary endocrine therapy), may be an option. A systematic review and meta-analysis published in JAMA Network Open on November 6, 2026 examined 29 studies and 22,821 women comparing this approach with surgery. However, the randomized evidence for the survival comparison comes from only six studies including 813 women. The hazard ratio for overall survival was 1.14 (95% confidence interval 0.98–1.33). In this article we explain why this result does not mean “the two paths are equal,” for whom treatment without surgery may be reasonable, and why the decision should not be made on age alone. You can find the basics of breast cancer in our breast cancer guide (in Turkish).
- What was found? In the randomized studies, no statistically significant difference was shown between primary endocrine therapy and surgery in overall survival (hazard ratio 1.14; 95% CI 0.98–1.33) or in breast cancer-specific survival (1.10; 0.83–1.46); the point estimates favored surgery.
- Does this mean they are equivalent? No. The confidence interval extends to a clear harm, and the evidence rests on only 813 patients; all of the randomized studies are from the tamoxifen era.
- Local control: Surgery keeps its clear advantage in controlling disease in the breast. With treatment without surgery, most progressions occur in the first five years and in the breast.
- For whom? Women with a strongly estrogen receptor-positive, slow-growing tumor, who are at high surgical risk because of frailty or other illnesses or who have a short expected lifespan, and who do not want surgery after being informed. The decision should not be made on age alone.
Why does this matter?
The world’s population is aging, and a large share of breast cancers are diagnosed after the age of 70 (cancer statistics in Türkiye [in Turkish]). Most tumors in this age group are hormone receptor-positive; that is, they are fed by estrogen and can respond well to hormone-suppressing drugs (hormone-positive breast cancer [in Turkish]). On the other hand, older women are underrepresented in clinical trials, so treatment recommendations for them are often based on data from younger patients.
Treatment decisions in older age become difficult from two directions. On one side there is the risk of undertreatment, that is, a treatable cancer not being treated adequately just because of age. On the other side is the risk of overtreatment, that is, performing an operation on a frail woman that brings more burden than benefit. The difference between calendar age and biological age is decisive here: some 85-year-old women are healthier than some 70-year-olds (chronological and biological age [in Turkish]).
What is primary endocrine therapy?
Primary endocrine therapy is a treatment that aims to keep hormone receptor-positive breast cancer under control without surgery, using hormone-suppressing drugs taken by mouth every day (most often aromatase inhibitors such as letrozole or anastrozole, sometimes tamoxifen). It aims not to eliminate the cancer but to stop its growth for a long time.
This approach differs from hormone therapy given to shrink the tumor before surgery (neoadjuvant endocrine therapy): here there is no planned operation. The tumor is followed with regular examinations and imaging. If the tumor shrinks or stays stable, treatment continues; if it starts to grow, the drug may be changed or surgery may be considered at that point.
Figure 1 · Two paths
Surgery or endocrine therapy alone
What does a hazard ratio of 1.14 mean?
The hazard ratio compares how often a certain event (here, loss of life) occurs in two groups. 1 means no difference between the two groups. In this meta-analysis, a value of 1.14 estimates that the risk of loss of life is on average 14% higher in women who received treatment without surgery than in those who had surgery. However, the 95% confidence interval runs from 0.98 to 1.33: the true effect could be anywhere from a small 2% advantage for treatment without surgery to a clear 33% difference in favor of surgery.
Because the interval includes 1, the result is considered “not statistically significant.” But this does not show that the two approaches are equal; it only says that a difference could not be demonstrated with certainty with so few patients. To say that two treatments are equivalent, the entire confidence interval would have to stay within a narrow, predefined region that can be considered clinically unimportant. That is not the case here (reading research results correctly [in Turkish]).
Figure 2 · How is a confidence interval read?
“No significant difference” and “equivalent” are not the same thing
What did the study examine?
Researchers at the University of Pittsburgh (UPMC Hillman Cancer Center) and Harvard searched for studies comparing primary endocrine therapy with surgery in women aged 65 and older with operable breast cancer that had not spread. The review included 29 studies published up to March 2026: 6 randomized controlled and 23 observational. The median age of the 22,821 women in total was 83; it was 77 in the randomized studies and 84 in the observational studies.
The researchers pooled survival only from the randomized studies. The reason matters: in observational studies, the women who do not have surgery are generally older, frailer and have more other illnesses. These women living shorter lives may be due not to the treatment but to their health at the start. Because of this “confounding by indication,” observational data are not suitable for comparing the two treatments fairly.
Where does the evidence come from?
Distribution of the 22,821 women included in the review by study type.
The survival comparison was made only with the randomized studies; in observational studies the women who do not have surgery are generally older and have more other illnesses, so they cannot be compared directly.
What was found?
Survival
In the pooled analysis of the randomized studies, the hazard ratio was 1.14 (95% CI 0.98–1.33) for overall survival and 1.10 (0.83–1.46) for breast cancer-specific survival. Neither was statistically significant, but the point estimates favored surgery. Of the six studies, only one (the CRC study in the United Kingdom) showed a significant survival difference in favor of surgery on its own. When the studies were removed from the analysis one at a time, the results always stayed in favor of surgery, but significance changed depending on which study was removed; in other words, the result is not robust. The 2014 Cochrane review had also reported that surgery plus hormone therapy reduced the risk of loss of life to a borderline significant degree compared with hormone therapy alone (hazard ratio 0.86; 95% CI 0.73–1.00).
Local control
Surgery keeps its clear advantage in controlling disease in the breast. In the Cochrane review, surgery plus hormone therapy reduced the risk of progression in the breast by about 72% compared with hormone therapy alone (hazard ratio 0.28). Even in the Nottingham II/EPS II study, which included strongly estrogen receptor-positive tumors, recurrence in the breast among women treated without surgery was 38% at 5 years and 43% at 10 years. Most progressions were seen in the breast and in the first five years. An important point: in a significant share of patients who progressed, the problem could be brought under control by changing the drug or by surgery at that point; uncontrolled local disease is seen less often in current studies (resistance to hormone therapy [in Turkish]).
Tumor biology is decisive
How long hormone therapy stays effective depends largely on the tumor’s biology. In tamoxifen-era studies in which hormone receptor status was unknown, the median time to disease progression was about 20 months. In contrast, in strongly estrogen receptor-positive tumors and in groups using aromatase inhibitors, this time exceeded 50 months, and in the Nottingham II/EPS II study it exceeded 60 months. In this group, in about 60% of women the response was still continuing at 10 years. Lobular-type tumors, which are more common in older age and are mostly strongly hormone receptor-positive, are also assessed separately in this respect (lobular breast cancer [in Turkish]). Features linked to a long-lasting response are a high estrogen receptor level, a low-grade tumor with low Ki-67 (slow-growing), and a small size (What is Ki-67? [in Turkish]). In some studies, the disappearance of tumor DNA in the blood (ctDNA) with treatment was also linked to a good response (ctDNA in breast cancer [in Turkish]).
How long does hormone therapy stay effective?
Median time to disease progression in women receiving endocrine therapy alone, in months.
The comparison across different studies is indirect; patient groups, prior treatments and follow-up times differ. In strongly ER-positive, slowly proliferating tumors the effect clearly lasts longer.
Competing risks: Breast cancer is not always the biggest threat
Perhaps the most instructive finding of the review concerns the causes of loss of life. In the randomized studies, during follow-up 28.8% of the women lost their lives to breast cancer and 47.3% to other causes. In the observational studies, which included older women, these rates were 12.2% and 36.5%. In groups where the median age was over 80 and other illnesses were common, loss of life from other causes reached 2–3 times that from breast cancer. This means that in a frail woman with other illnesses, the benefit surgery can provide may remain limited.
Figure 3 · Causes of loss of life
In randomized and observational studies
How should we read the results?
- Only a small part of the evidence is randomized: Only 813 (3.6%) of the 22,821 women come from randomized studies. The wide confidence intervals stem from this.
- Old drug, old selection: Tamoxifen was used in all of the randomized studies, and in most the hormone receptor status of the tumor was unknown. With the aromatase inhibitors used today and better patient selection, results may differ; this could work in either direction.
- Estimated values: The hazard ratios of four studies were recalculated from published survival curves; this is an additional source of uncertainty.
- Quality of life was not measured: Quality of life and side effects were not reported in the review; yet in older age these matter at least as much as survival for the decision.
- The proposed framework is not validated: The authors’ selection framework based on tumor biology, frailty and other illnesses is conceptual; it needs to be tested in prospective studies (reading meta-analyses [in Turkish]).
Who is treatment with endocrine therapy alone suitable for?
The review’s authors and the European recommendations meet at the same point: the decision should rest not on calendar age but on three factors assessed together. The first is tumor biology: strongly estrogen receptor-positive, HER2-negative, low-grade and slow-growing tumors tend to respond to hormone therapy for a long time. The second is the person’s health status: conditions such as frailty, serious heart or lung disease and dementia increase surgical risk and shorten expected lifespan. In the SIOG and EUSOMA recommendations, treatment without surgery is described as an alternative for women with a strongly estrogen receptor-positive tumor and an expected lifespan of less than about 5 years. The third is the person’s preference: the choice of a woman who, after being informed, does not want surgery should be respected.
Figure 4 · The three pillars of the decision
Tumor, health status and preference
Figure 5 · For whom may it be suitable, and for whom not?
A practical summary
Surgery is not always a major procedure
For many older women, surgery can be lighter than expected. Breast-conserving surgery is often short and in some centers can be done under local anesthesia. In low-risk women over 70 whose armpit lymph nodes look normal clinically, an intervention in the armpit (sentinel lymph node biopsy) is often not needed (is removing armpit lymph nodes necessary? [in Turkish], sentinel lymph node biopsy (in Turkish)). Avoiding radiotherapy after surgery is also a reasonable option in low-risk, hormone receptor-positive tumors: in the PRIME II study, although recurrence in the breast at 10 years was 9.5% versus 0.9% in women who did not receive radiotherapy, no difference was seen in overall survival. Chemotherapy, in turn, is often not needed in this low-risk group (who does not need chemotherapy? [in Turkish]).
So the choice can be made not between “major surgery or no surgery at all,” but between a short, light operation and pill treatment alone. Given the advantage of surgery for local control, surgery remains the standard option for women who can safely have it (breast-conserving surgery [in Turkish]).
Figure 6 · Decision steps
Five steps in breast cancer in older age
If treatment without surgery is chosen: follow-up and side effects
Treatment without surgery does not mean “starting the drug and waiting.” In the first months of treatment, regular examination and ultrasound are used to see whether the tumor is shrinking. No response in the first few months, or growth, is a sign that the drug should be changed or surgery reconsidered. In women who respond, check-ups are continued at less frequent intervals.
Aromatase inhibitors can cause joint and muscle pain, hot flashes and bone loss; therefore bone density should be measured, vitamin D and calcium levels assessed and, if needed, bone-protecting treatment given (exercise and fracture risk [in Turkish]). Tamoxifen carries a risk of clots and changes in the lining of the uterus. Since older women often use many drugs, drug interactions and regular medication intake should also be checked (drug interactions [in Turkish]). Regular movement supports both adherence to treatment and quality of life by preserving muscle strength and balance (exercise and rehabilitation [in Turkish]).
Figure 7 · Follow-up without surgery
Confirming with regular check-ups that the effect continues
The Situation in Türkiye
- Drugs: Letrozole, anastrozole, exemestane and tamoxifen are licensed in Türkiye and widely used in breast cancer treatment; ask your treatment team about drug choice and reimbursement conditions (recent developments in breast cancer treatment [in Turkish]).
- Geriatric assessment: Short, easy-to-use tools for frailty screening (for example the G8 scale) can be used in outpatient settings; when a detailed geriatric assessment is needed, support should be sought from centers with geriatric units.
- Multidisciplinary decision: In older women, treatment choice should be discussed in a board that includes general surgery, medical oncology, radiation oncology and, if possible, geriatric specialists.
- Beware of undertreatment: It is important that older women who could safely have surgery are not denied standard treatment just because of their age; it has also been shown in other cancers that effective treatments can benefit people in older age (chemotherapy in older age [in Turkish]).
Questions you can ask your physician
- What are my tumor’s estrogen receptor level, grade and Ki-67 value; is the likelihood of a long response to hormone therapy high?
- How risky is surgery for me; would a shorter operation under local anesthesia be possible?
- Is an intervention in the armpit and radiotherapy necessary in my case?
- If I choose treatment without surgery, how often should I come for check-ups; what will be done if there is progression?
- What should I watch for regarding interactions with my other drugs and my bone health?
- “The study showed that surgery and pill treatment are equal.” No. The difference was not statistically significant, but the confidence interval extends to a clear harm and the evidence rests on only 813 patients.
- “Surgery is not done over the age of 80.” No. The decision rests not on age but on health status, tumor biology and preference. Healthy older women can benefit from surgery.
- “Treatment without surgery cures the cancer completely.” No. The aim is to keep the tumor under control for a long time; in some women progression occurs over time, and a change of drug or surgery may be needed.
- “If pill treatment is chosen, no check-ups are needed.” No. Regular examination and imaging are needed to confirm the treatment is working.
- “Every breast cancer responds to pill treatment.” No. This approach works only in hormone receptor-positive tumors, and with the best results in strongly estrogen receptor-positive, slow-growing tumors (tumor biology [in Turkish]).
Frequently Asked Questions
- What is primary endocrine therapy?
- It is a treatment that aims to keep hormone receptor-positive breast cancer under control without surgery, using hormone-suppressing drugs such as letrozole, anastrozole or tamoxifen taken every day. It aims not to eliminate the cancer but to stop its growth for a long time.
- In older age, is hormone therapy enough instead of surgery in breast cancer?
- For some women, yes. In the randomized studies no significant difference in survival could be shown (hazard ratio 1.14; 95% CI 0.98–1.33), but this is not proof of equivalence, and surgery controls disease in the breast better. The choice should be made according to tumor biology and health status.
- Who is hormone therapy without surgery suitable for?
- It may be suitable for women who have a strongly estrogen receptor-positive, slow-growing tumor; who are at high surgical risk because of frailty or serious other illnesses, or have a short expected lifespan; or who do not want surgery after being informed. Age alone is not a sufficient criterion.
- What happens if hormone therapy does not work?
- If the tumor starts to grow, the drug may be changed or surgery may be performed at that point. Surgery is often still possible and in some cases can be done under local anesthesia. That is why regular check-ups are important.
Glossary
- Primary endocrine therapy
- Breast cancer treatment carried out with hormone-suppressing drugs alone, without surgery.
- Hormone receptor-positive
- Breast cancer whose growth is stimulated by estrogen or progesterone and that can respond to hormone therapy.
- Aromatase inhibitor
- A group of drugs that reduce estrogen production in the body after menopause; letrozole, anastrozole and exemestane.
- Tamoxifen
- A hormone therapy drug that blocks the effect of estrogen on breast cancer cells.
- Hazard ratio (HR)
- A measure comparing the rate at which an event occurs over time in two groups; 1 means no difference.
- Confidence interval
- The range of values in which the true effect most likely lies.
- Local control
- Preventing the tumor from growing or coming back in and around the breast.
- Ki-67
- A pathology marker showing how fast tumor cells are multiplying.
- Frailty
- Reduced resilience to stress and treatments as age-related physiological reserves decline.
- Competing risk
- The probability of loss of life from causes other than the disease of interest; in older age it can limit the benefit of treatment.
DROZDOGAN Academy Commentary
This meta-analysis does not give a single answer to the question “surgery or pills?” in breast cancer treatment in older age; it asks the right question: by which path does this woman, with this tumor, benefit more?
⚡ Why it matters
In a rapidly aging society, avoiding both undertreatment and overtreatment in older women is becoming increasingly important. The review supports an approach based on biology and frailty rather than decisions based on age.
✅ Strengths
A broad literature search; the survival comparison made only with randomized studies; detailed treatment of competing risks and tumor biology.
⚠️ Limitations
The randomized evidence rests on only 813 patients and the tamoxifen era; the protocol was not registered in advance; quality of life and side effects were not reported; the proposed selection framework is not validated.
🩺 In practice
For older women who can safely have surgery, we recommend a short, light operation, without an armpit intervention or radiotherapy if appropriate. For women with a strongly estrogen receptor-positive tumor who are frail or do not want surgery, we offer treatment without surgery with an aromatase inhibitor, together with a regular follow-up plan, as a reasonable option.
❓ Open questions
What will current randomized studies with aromatase inhibitors and well-selected patients show? Which biological markers best predict a long-lasting response? Which path is more advantageous in terms of quality of life?
Conclusion: In hormone receptor-positive breast cancer in older age, surgery remains the standard option for local control. Endocrine therapy without surgery is a valuable alternative for women who are biologically suitable and who are not suitable for surgery or do not want it; however, the decision should not be made on age alone.
- This article was prepared in November 2026.
- The information is taken from the systematic review and meta-analysis published in JAMA Network Open on November 6, 2026, from the 2014 Cochrane review and from the SIOG/EUSOMA recommendations.
- Although the abstract of the review states estrogen receptor-positive disease, the methods section states that no restriction was made by hormone receptor status; in most of the randomized studies the receptor status was unknown.
- The chart showing times to progression in different studies is an indirect comparison. The drawings are simplified. The Academy commentary is ours.
- This article is not medical advice; make your health decisions together with your physician.
References
- Carleton N, Zou J, Mu Y, et al. Primary endocrine therapy vs upfront surgery for older women with estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Netw Open 2026;9(11):e2643218. jamanetwork.com
- Hind D, Wyld L, Reed MW. Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus). Cochrane Database Syst Rev 2014;(5):CD004272. cochranelibrary.com
- Biganzoli L, Battisti NML, Wildiers H, et al. Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG). Lancet Oncol 2021;22:e327-e340. institut-curie.org
- Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer (PRIME II). N Engl J Med 2023;388:585-594. doi.org
- Cochrane. Surgery versus primary endocrine therapy for elderly women with operable primary breast cancer (plain language summary). cochrane.org
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