DCIS, a non-invasive condition in which abnormal cells are confined to the milk ducts, accounts for roughly one in four breast cancers detected through screening programmes. Standard treatment options include mastectomy or breast-conserving surgery (BCS), with or without adjuvant radiotherapy, and in some cases endocrine therapy with drugs such as tamoxifen or aromatase inhibitors to reduce the risk of recurrence. Because approximately 65 to 80 percent of DCIS lesions are oestrogen receptor positive, knowing a tumour’s ER status is central to deciding whether hormone therapy is appropriate. Yet, as the new study demonstrates, ER testing for DCIS was performed in only 15.4 percent of the 5,813 women included in the cohort.

The researchers drew their data from the Breast Cancer Foundation National Register, which began collecting information in Auckland and Waikato in 2000, expanded to Christchurch in 2009 and Wellington in 2010, and achieved nationwide coverage only from 2020 onwards. By linking the register to New Zealand’s national Pharmaceutical Collection database through encrypted National Health Index numbers, the team could identify who was dispensed tamoxifen or aromatase inhibitors after a DCIS diagnosis. Statistical analyses employed multivariable logistic regression to identify factors associated with ER testing and cumulative incidence functions, with death treated as a competing risk, to estimate the probability of breast cancer events over time.

The headline finding is geographic. Of the 894 women who had an ER test on record, 65.6 percent were treated in the Waikato region, home to a well-established breast cancer research infrastructure and one of New Zealand’s two original breast screening pilot programmes. In Waikato, ER testing rose sharply from 35 percent in the late 1990s to 82.4 percent by 2003 and remained high, reaching 84.8 percent in 2022. Everywhere else, testing stayed stubbornly low, creeping from just 4.5 percent in 2000 to 7.1 percent in 2022. The investigators attribute Waikato’s exceptional performance to the participation of local clinical centres in international trials evaluating endocrine therapy for DCIS, including the UK/ANZ DCIS trial and the IBIS-II DCIS trial, which exposed clinicians there to the evidence base early and embedded testing into routine care.

The factors associated with receiving an ER test also differed dramatically by region, offering a window into contrasting models of care. In Waikato, women who received adjuvant radiotherapy after breast-conserving surgery were more likely to be tested, a pattern the authors interpret as reflecting local protocols that promoted both treatments in tandem rather than selective ordering by individual clinicians. Elsewhere in the country, testing appeared highly selective: older women, Māori women, those presenting with symptoms rather than through screening, and those with larger DCIS lesions exceeding 20 millimetres were more likely to be tested, suggesting clinicians ordered the test only when they believed the result would influence management. Nationally, the overall testing rate rose from 11.1 percent in 2000 to a peak of 23.3 percent in 2006 before drifting back down to 13.9 percent in 2022.

Among the 729 women whose DCIS was confirmed as ER positive, only 183, or 25.1 percent, actually initiated endocrine therapy, and more than 80 percent of those initiations occurred in Waikato. Tamoxifen was the most common first-line treatment, used by 58.5 percent of women starting therapy, followed by aromatase inhibitors at 38.3 percent. Consistent with shifts seen internationally after the NSABP B-35 trial suggested anastrozole outperformed tamoxifen in postmenopausal women, aromatase inhibitor use in Waikato climbed steadily, exceeding tamoxifen after 2018 and rising from 12.5 percent of initiations in the mid-2000s to 55 percent by 2022. Overall initiation of endocrine therapy in Waikato grew from 20 percent in 2000–2001 to 62.5 percent in 2022.

Does the hormone therapy actually help? After a median follow-up of 4.8 years, women with ER-positive DCIS who received endocrine therapy showed the lowest cumulative risk of any breast cancer event, but the differences between groups did not reach statistical significance, likely because the number of treated patients and events was simply too small to detect a benefit. The authors caution that these results do not exclude a clinically meaningful effect. Supporting evidence from prior research suggests that good adherence reduces recurrence, that at least two years of treatment decreases second breast events, and that adding endocrine therapy to breast-conserving surgery lowers the risk of subsequent invasive breast cancer compared with surgery alone. For a subset of Waikato women with documented therapy use of at least two years, the five-year cumulative incidence of a breast cancer event was just 6.3 percent, though this estimate rested on very few events.

The international context makes New Zealand’s numbers stand out even more sharply. In the United States, ER testing for DCIS surged from 17.5 percent in the early 2000s to 93.1 percent by 2012–2014, propelled by the 2000 approval of tamoxifen for DCIS following the NSABP B-24 trial. European testing rates range from 30 to 85 percent. Since 2020, both the ASCO/CAP guideline and the National Comprehensive Cancer Network have recommended ER testing for all DCIS patients to guide endocrine therapy decisions. New Zealand’s own early breast cancer guideline, last updated in 2009, recommends endocrine therapy for ER-positive invasive cancers but leaves the decision for ER-positive DCIS to individual circumstances, leaving clinicians without a clear national mandate for testing.

The study’s authors argue that the regional variation they documented is not an argument for exporting Waikato’s model wholesale, but rather evidence that nationally consistent guidelines and clinical pathways are urgently needed. Without standardised ER testing, they note, clinicians and patients cannot make informed decisions about whether the potential recurrence-reduction benefits of endocrine therapy, weighed against side effects such as aromatase inhibitor-related musculoskeletal symptoms, are worth pursuing in an individual case. Options such as low-dose tamoxifen, which showed comparable efficacy with improved tolerability in the TAM-01 trial, may widen the appeal of treatment for patients prioritising quality of life. Greater clinician participation in clinical trials, the researchers suggest, could simultaneously strengthen local evidence and keep practitioners engaged with emerging data.

Limitations temper some conclusions. Registry data capture began at different times in different regions, and nationwide coverage was achieved only in 2020, making endocrine therapy initiation numbers outside Waikato too sparse for trend analysis. Patient preferences regarding adjuvant therapy were unavailable, and the observed higher likelihood of testing among Māori women outside Waikato may reflect unmeasured local practice patterns rather than true differences in tumour biology. Nevertheless, as the first population-based study of ER testing and endocrine therapy for DCIS in New Zealand, the work delivers a clear message: a two-decade evidence gap persists in routine care, and closing it will require updated national guidelines, standardised receptor testing, and a broader culture of clinical research participation to ensure that women with DCIS everywhere benefit from treatments proven in trials.

Subject of Research: Oestrogen receptor testing and adjuvant endocrine therapy use in ductal carcinoma in situ in New Zealand

Article Title: Oestrogen receptor testing and initiation of adjuvant endocrine therapy in women with ductal carcinoma in situ: a population-based study

Article References: Oestrogen receptor testing and initiation of adjuvant endocrine therapy in women with ductal carcinoma in situ: a population-based study. (n.d.). https://doi.org/10.1007/s10549-026-08072-7

Image Credits: AI Generated

DOI: 10.1007/s10549-026-08072-7

Keywords: ductal carcinoma in situ, oestrogen receptor testing, endocrine therapy, tamoxifen, aromatase inhibitors, breast cancer, New Zealand, regional variation, population-based study, clinical trials, recurrence, guidelines

Breast cancer remains the most prevalent form of cancer among women worldwide and constitutes more than 15% of all new cancer diagnoses in the United States alone. The pathological entities DCIS and LCIS are characterized by abnormal cells confined respectively within the breast ducts and lobules, and while non-invasive themselves, have been strongly implicated as precursors to invasive breast cancer. However, clinicians have long grappled with the challenge of discerning which cases of DCIS and LCIS will progress to invasive disease, complicating treatment decisions and often leading to overtreatment or undertreatment.

The PRS₃₁₃ test quantifies breast cancer risk by aggregating the effects of 313 single-nucleotide polymorphisms (SNPs) that have previously been associated with breast cancer susceptibility. These genetic markers collectively provide a polygenic risk profile that reflects an individual’s inherited predisposition. Prior validation of PRS₃₁₃ in populations of women with no prior cancer history demonstrated its capacity to stratify breast cancer risk effectively. This study, relentlessly spearheaded by Jasmine Timbres and senior author Professor Elinor J. Sawyer, positions PRS₃₁₃ as a potentially transformative tool for risk stratification specifically in patients already diagnosed with DCIS or LCIS.

To rigorously evaluate the predictive utility of PRS₃₁₃ in in situ breast disease, the research team delved into comprehensive datasets from two major UK-based cohorts — the ICICLE (ductal carcinoma in situ) and GLACIER (lobular carcinoma in situ) studies. Cumulatively, these databases provided genetic and longitudinal clinical follow-up information for 2,169 women with DCIS and 185 women with LCIS. Applying sophisticated statistical models, the team analyzed the association between patients’ PRS₃₁₃ scores and their subsequent risk of developing invasive breast cancer over time.

The results illuminate critical distinctions in risk profiles based on PRS₃₁₃ quartiles and anatomical tumor locations. Among women with DCIS, those within the highest PRS₃₁₃ quartile exhibited a twofold increase in the likelihood of developing contralateral breast cancer—the manifestation of invasive disease in the breast opposite the site of the initial in situ lesion. Interestingly, the predictive value of PRS₃₁₃ did not extend significantly to ipsilateral breast cancer in DCIS patients, an observation that underscores the complex biology and progression pathways of breast neoplasms.

Conversely, the data revealed a strong dose-response relationship in LCIS patients: as PRS₃₁₃ scores increased, so did the risk of ipsilateral invasive breast cancer, with risk more than doubling per unit increase in the score. These findings suggest that the genetic architecture captured by PRS₃₁₃ may differentially influence localized tumor progression depending on in situ tumor subtype, potentially guiding subtype-specific surveillance and intervention strategies.

A notable aspect of the study is the interaction between family history and polygenic risk scores. Women carrying a familial predisposition to breast cancer exhibited a markedly amplified risk associated with higher PRS₃₁₃ values, surpassing a threefold increase for ipsilateral cancer following LCIS. Remarkably, this risk escalated to fourfold among women without prior mastectomy or radiotherapy, highlighting the importance of integrating genetic risk scores with familial information and treatment history to refine prognostication.

Professor Sawyer elaborated on the clinical implications, emphasizing that LCIS, traditionally considered lower risk than DCIS and often managed conservatively without surgery or hormone therapy, may warrant reconsideration for more aggressive treatment in patients with elevated polygenic risk and familial background. Such tailored therapies could significantly reduce progression to invasive cancer, improving patient outcomes and quality of life.

The study pioneers a paradigm shift in breast cancer risk assessment by advocating a comprehensive approach that transcends histopathological evaluation. As Timbres elucidates, employing PRS₃₁₃ alongside traditional diagnostics offers a nuanced risk profile that empowers women with DCIS or LCIS to make more informed choices regarding their management options, balancing efficacy and potential overtreatment.

Despite promising insights, the study acknowledges inherent limitations. The PRS₃₁₃ was originally optimized for invasive breast cancer risk prediction, thus it may not capture genetic variants specifically implicated in in situ lesions that remain to be discovered. Additionally, the limited LCIS sample size constrains the statistical power to detect more subtle associations, warranting validation in larger, more diverse populations.

Funding support for the research was provided by Breast Cancer Now, Cancer Research UK, and the Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. Both lead and senior authors report no conflicts of interest, underscoring the study’s integrity and scientific rigor.

These compelling findings herald a new frontier in precision oncology, where polygenic risk scoring complements existing histological and clinical parameters to tailor breast cancer prevention and treatment strategies. As further validation and technological advancements unfold, integrating PRS₃₁₃ into clinical workflows may revolutionize how clinicians assess risk and personalize care for women with in situ breast disease, ultimately mitigating the burden of invasive breast cancer on a global scale.

Subject of Research: Breast cancer risk prediction using a 313-SNP polygenic risk score in patients with ductal and lobular carcinoma in situ

Article Title: Breast Cancer Polygenic Risk Score Associated With Outcomes After In Situ Breast Disease

News Publication Date: 1-Oct-2025

Web References:

• Cancer Epidemiology, Biomarkers & Prevention
• ICICLE Study
• GLACIER Study
• PRS₃₁₃ Validation Study

References: DOI: 10.1158/1055-9965.EPI-25-0529

Keywords: Breast cancer, Polygenic risk score, DCIS, LCIS, Genetic risk, Cancer epidemiology, Personalized medicine, In situ breast disease

Duavee’s dual action tackles menopausal discomfort while exhibiting biologically significant effects on breast tissue. Postmenopausal women diagnosed with ductal carcinoma in situ (DCIS), a non-invasive breast condition widely regarded as a precursor to invasive breast cancer, participated in the trial. DCIS affects approximately 60,000 women annually in the United States alone, representing a substantial population at risk. This phase 2 trial randomized 141 women across ten clinical sites to receive either Duavee or a placebo during a critical window between diagnosis and surgical intervention.

The scientific rationale behind this study centers on the modulation of hormone receptors in breast tissue. Estrogens influence cellular proliferation, and selective estrogen receptor modulators like bazedoxifene are designed to mitigate estrogen’s unwanted effects in the breast while providing beneficial effects elsewhere in the body, such as bone preservation. By combining these agents, Duavee offers a nuanced hormonal environment that was observed to reduce markers indicative of cellular proliferation in breast tissue samples, which are highly predictive of the risk of malignant transformation.

According to Dr. Swati Kulkarni, the lead investigator and a professor of breast surgery at Northwestern University Feinberg School of Medicine, the reduction in cell growth rates observed in the Duavee-treated group is a promising biomarker change indicative of hindered cancer progression pathways. This represents a significant breakthrough as current medications for breast cancer prevention often involve considerable side effects that lead many women to forego prophylactic treatment.

Critically, Duavee’s tolerability profile in this trial appeared favorable. Unlike other hormone-based preventive therapies known for inducing menopausal symptom exacerbation or other systemic side effects, participants receiving Duavee did not report a decline in quality of life. This tolerability could lead to improved adherence and acceptance among women facing the challenge of balancing menopausal management with breast cancer risk reduction.

The target population for this intervention encompasses women with a history of high-risk breast lesions, including atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS), as well as prior diagnoses of DCIS. These conditions elevate the lifetime risk of invasive breast cancer substantially. Women in this demographic group typically have limited options for hormone therapy during menopause due to concerns about triggering cancerous changes, making Duavee a potentially valuable therapeutic alternative.

The mechanism by which Duavee affects breast tissue involves selective modulation at the estrogen receptor level. Conjugated estrogens provide hormone replacement to alleviate menopausal symptoms, while bazedoxifene acts as an estrogen receptor antagonist specifically in breast and uterine tissue, preventing potential proliferative effects. This complex interplay may disrupt the estrogen-driven pathways responsible for cellular overgrowth, thereby curbing neoplastic progression without compromising systemic estrogen benefits.

This trial’s methodology included administering Duavee or placebo for approximately four weeks, a relatively brief preoperative period allowing precise examination of acute biological effects on breast tissue sampled during surgery. Despite the short duration, the significant decrease in cell proliferation markers underscores a robust biological response, suggesting the potential for even greater benefits with extended therapy, pending future studies.

While these results are compelling, Dr. Kulkarni emphasizes the necessity for larger scale trials with extended follow-up to validate long-term efficacy and safety before recommending Duavee as a standard preventive therapy. The existing FDA approval and widespread clinical availability of Duavee, however, expedite the potential translational impact should future research corroborate these findings.

The broader implications of this research are profound, as it bridges menopausal symptom management and cancer prevention—two domains often treated disparately despite their clinical intersection. The availability of a well-tolerated, dual-purpose medication could revolutionize the approach to care in a vulnerable demographic of postmenopausal women at elevated breast cancer risk.

This study also exemplifies the value of repurposing existing drugs with well-characterized safety profiles, potentially accelerating access to new clinical applications without the lengthy drug development timelines typically required. Such strategies are especially important in oncology, where prevention remains a critical yet underutilized avenue.

In summary, the Northwestern-led clinical trial presents a promising new frontier in breast cancer prevention. Duavee’s ability to slow cellular proliferation in DCIS lesions, coupled with its menopausal symptom relief and favorable side effect profile, highlights its potential as a transformative option. As more comprehensive data emerges, this therapy may become a cornerstone in reducing invasive breast cancer incidence among high-risk postmenopausal women, ultimately improving both longevity and quality of life.

Subject of Research: The investigation into Duavee’s effectiveness in preventing invasive breast cancer progression in postmenopausal women with DCIS.

Article Title: Common Menopause Drug Duavee Shows Potential to Prevent Invasive Breast Cancer in High-Risk Women

News Publication Date: June 1, 2025

Web References:

• Northwestern Medicine Faculty Profile: Dr. Swati Kulkarni
• Clinical Trial Registration: NCT02694809
• ASCO Annual Meeting Presentation Details: ASCO 2025 Meeting
• Breast Cancer Research Foundation on DCIS: About DCIS

Keywords: Breast cancer, DCIS, menopausal symptoms, hormone therapy, conjugated estrogens, bazedoxifene, hormone receptor modulation, cancer prevention, selective estrogen receptor modulator, postmenopausal women, cell proliferation, hormonal biology.