Ovarian Suppression Adds Little Survival Benefit After Modern HER2 Therapy, Study Finds

For young women facing breast cancer, few treatment questions are as consequential — or as contested — as whether to shut down the ovaries. A new retrospective study from Istanbul now adds a carefully caveated data point to that debate, suggesting that adding ovarian function suppression to standard hormone therapy may offer less benefit than many clinicians assume, at least for premenopausal patients whose tumors are both hormone receptor-positive and HER2-positive and who have already received modern anti-HER2 treatment before surgery.

The research, conducted by a team at the University of Health Sciences Prof. Dr. Cemil Tascioglu City Hospital and published in BMC Cancer, examined 138 premenopausal women with non-metastatic, hormone receptor-positive, HER2-positive breast cancer. All of the patients had undergone neoadjuvant therapy — treatment given before surgery — built around anti-HER2 agents, followed by surgical removal of their tumors between 2015 and 2024. The investigators then split the cohort according to whether the women received ovarian function suppression, or OFS, during the adjuvant period, the phase of care that follows surgery and is designed to mop up any remaining cancer cells.

The biology behind the question is straightforward. In premenopausal women, the ovaries are the dominant source of estrogen, the hormone that fuels the growth of hormone receptor-positive tumors. Blocking ovarian output — typically with gonadotropin-releasing hormone agonists that effectively switch the ovaries off — dramatically lowers circulating estrogen. Combined with drugs such as tamoxifen, which blocks estrogen receptors on cancer cells, or aromatase inhibitors, which block estrogen synthesis in peripheral tissues, ovarian suppression is intended to starve any residual disease of its principal growth signal. In HER2-negative disease, landmark trials have shown clear benefits from this strategy. But HER2-positive tumors behave differently, and the arrival of potent anti-HER2 therapies such as trastuzumab has transformed outcomes, raising the possibility that the incremental value of ovarian suppression has shrunk.

That possibility is precisely what the Turkish team set out to test. Of the 138 patients, 60 — or 43.5 percent — received ovarian function suppression as part of their adjuvant endocrine treatment. The remaining 78 did not. The researchers tracked three primary endpoints: disease-free survival, which measures the time before cancer returns anywhere in the body; distant disease-free survival, which focuses specifically on spread to distant organs; and overall survival. They also assessed pathological complete response, abbreviated pCR, as a secondary endpoint. A pCR means that when pathologists examine the tissue removed at surgery, they find no invasive cancer in the breast and no cancer in the sampled lymph nodes — a marker widely regarded as one of the strongest predictors of long-term cure.

The headline numbers were striking in places. Overall, 42 percent of the entire cohort achieved a pathological complete response, a figure that underscores just how powerful neoadjuvant anti-HER2 therapy has become. After a median follow-up of 56 months, 20 patients — 14.5 percent — had experienced a recurrence or developed metastatic disease, and 11 patients, or 8 percent, had died. Those figures, sobering as they are, reflect the reality of a disease subtype that remains challenging even in the modern therapeutic era.

When the investigators compared the two groups, the differences were modest at best. Five-year overall survival was 93.9 percent among women who received ovarian suppression versus 85.8 percent among those who did not — a numerical gap, but one that did not reach statistical significance, with a p-value of 0.4. Disease-free survival was essentially identical between the arms: 80.7 percent with ovarian suppression and 81.3 percent without, yielding a p-value of 0.9. Distant disease-free survival followed the same pattern. In other words, on the primary measures of whether cancer came back or whether patients lived, the addition of ovarian suppression made no statistically detectable difference in this cohort.

The most intriguing signal emerged when the researchers stratified patients by their response to neoadjuvant therapy. Women who achieved a pathological complete response had excellent outcomes regardless of whether their ovaries were subsequently suppressed — their five-year overall survival was a remarkable 100 percent. This finding reinforces a growing consensus in oncology: for patients whose tumors vanish under preoperative anti-HER2 treatment, the prognosis is already so favorable that additional endocrine intensification may contribute little. The residual-disease group told a more nuanced story. Among women who still had detectable cancer at surgery, ovarian suppression was associated with numerically higher overall survival — 89.9 percent versus 77.6 percent — but this apparent advantage did not translate into a disease-free survival benefit, and the difference was not statistically significant.

To account for the possibility that the two groups differed in ways that could confound the comparison — differences in tumor size, nodal involvement, grade, or the type of endocrine therapy received — the team performed multivariate analysis, a statistical technique that adjusts for multiple variables simultaneously. The result was unambiguous: ovarian function suppression showed no independent association with disease-free survival, distant disease-free survival, or overall survival once other factors were taken into account. The authors are careful to note, however, that the study’s statistical power was limited. With 138 patients and relatively few events — 20 recurrences and 11 deaths — the analysis simply cannot exclude a modest benefit that a larger trial might detect.

Another critical caveat concerns the composition of the endocrine therapy itself. The cohort was predominantly treated with tamoxifen, the selective estrogen receptor modulator that has long been the backbone of adjuvant therapy in premenopausal women. Whether ovarian suppression paired with aromatase inhibitors — a more aggressive regimen that eliminates nearly all estrogen production — would perform differently cannot be answered by this dataset. The authors explicitly caution that, given the limited statistical power and the tamoxifen-dominated treatment landscape, their findings should be interpreted with care, and they call for prospective studies to define the role of ovarian suppression in this population with the rigor that only randomized designs can provide.

For clinicians and patients, the practical message is one of individualized decision-making rather than a blanket rule. Ovarian suppression is not a free intervention: it induces a premature, often abrupt menopause, bringing hot flashes, bone density loss, sexual dysfunction, and potential effects on fertility and quality of life. If a young woman achieves a pathological complete response after neoadjuvant anti-HER2 therapy, the data suggest her prognosis is excellent without intensification, and she and her physician may reasonably weigh the burden of suppression against its uncertain benefit. For those with residual disease, the numerically better overall survival observed with suppression — though not statistically significant — may still inform a shared decision, particularly for patients with other high-risk features. What this single-center experience ultimately demonstrates is that the era of effective anti-HER2 therapy has changed the calculus of endocrine intensification, and that the questions guiding treatment for premenopausal, hormone receptor-positive, HER2-positive breast cancer are now as much about avoiding overtreatment as about maximizing it. Larger, prospective trials will be needed to settle the matter definitively, but for now, this study offers a data-driven reminder that more intensive therapy is not always better therapy.

Subject of Research: Ovarian function suppression in adjuvant endocrine therapy for premenopausal hormone receptor-positive, HER2-positive breast cancer after neoadjuvant anti-HER2 therapy

Article Title: The effect of adding ovarian function suppression to adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive, HER2-positive breast cancer who have undergone neoadjuvant therapy: a single-center experience

Article References: Aydin, O., Dogan, H. G. Y., Sonusen, S. D., Erciyestepe, M., Ozturk, A. E., Buyukkuscu, A., Isleyen, Z. S., & Erturk, K. (2026). The effect of adding ovarian function suppression to adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive, HER2-positive breast cancer who have undergone neoadjuvant therapy: a single-center experience. BMC Cancer, 26(1), Article 1140. https://doi.org/10.1186/s12885-026-17017-8

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17017-8

Keywords: breast cancer, HER2-positive, hormone receptor-positive, ovarian function suppression, neoadjuvant therapy, adjuvant endocrine therapy, pathological complete response, disease-free survival, overall survival, tamoxifen, premenopausal, oncology