Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial

Bartlett, John M.S.; Sgroi, Dennis; Treuner, Kai; Zhang, Y; Ahmed, Ikhlaaq; Piper, Tammy; Salunga, Ranelle; Brachtel, Elena F.; Pirrie, Sarah; Schnabel, Catherine A.; Rea, Daniel

doi:10.1093/annonc/mdz289

Cited by 146 publications

(147 citation statements)

References 36 publications

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“…High vs Low likelihood of benefit from extended endocrine therapy that is reported separately from the prognostic results (19,21,22).…”

Section: Component Of Bci [Bci (H/i)] Is Based On the H/i Ratio And Pmentioning

confidence: 99%

“…Author Manuscript Published OnlineFirst on October 27, 2020; DOI: 10.1158/1078-0432.CCR- Previous clinical validation studies for prediction of extended endocrine benefit and outcome have demonstrated significant interaction between BCI (H/I) and extended endocrine therapy with letrozole or tamoxifen following initial tamoxifen treatment (19,22). A key question regarding BCI clinical utility is the biomarker effect in postmenopausal patients treated with a contemporary standard of care that includes an AI component as part of primary adjuvant treatment.…”

Section: Component Of Bci [Bci (H/i)] Is Based On the H/i Ratio And Pmentioning

confidence: 99%

“…The IDEAL translational cohort (N=908) showed a 4.9% absolute benefit in the reduction of 10-year risk of RFI events with 10 years vs 7.5 years of endocrine therapy (HR 0.69, 95% CI 0.47-1.03; P=0.07). Powering assumptions included a 5% sample testing failure rate and that 40% of patients would be classified as BCI (H/I)-High based on previous studies (19,22). At 80% power, it was estimated that a total of 768 patients would be required to detect the benefit in BCI (H/I)-High patients at the 5% significance level.…”

Section: Statistical Considerationsmentioning

confidence: 99%

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Breast Cancer Index Predicts Extended Endocrine Benefit to Individualize Selection of Patients with HR+ Early-stage Breast Cancer for 10 Years of Endocrine Therapy

Noordhoek

Treuner

Putter

et al. 2021

Clinical Cancer Research

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Individualized selection of patients with early stage hormone receptor positive (HR+) breast cancer for extended endocrine therapy (EET) are required to balance modest gains in outcome with toxicities of prolonged use. This study examined the Breast Cancer Index (BCI) [HOXB13/IL17BR ratio (H/I)] as a predictive biomarker of EET benefit in patients from the Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL) trial. Experimental Design: BCI was tested in primary tumor specimens from 908 patients randomized to receive 2.5 vs 5 years of extended letrozole. The primary endpoint was recurrence-free interval (RFI). Cox models and likelihood ratios tested the interaction between EET and BCI (H/I). Results: BCI (H/I)-High significantly predicted benefit from extended letrozole in the Overall cohort (HR 0.42, 95% CI 0.21-0.84; P=0.011) and Any AI subset (HR 0.34, 0.16-0.73; P=0.004), whereas BCI (H/I)-Low patients did not derive significant benefit (HR 0.95, 0.58-1.56; P=0.84, HR 0.90, 0.53-1.55; P=0.71, respectively); treatment to biomarker interaction was significant (P=0.045, P=0.025, respectively). BCI identified ~50% of patients with clinically high-risk disease that did not benefit, and with clinically low-risk disease that derived significant benefit, from an additional 2.5 years of EET. Conclusions: BCI (H/I) predicted preferential benefit from 5 vs 2.5 years of EET and identified patients with improved outcomes from completing 10 years of adjuvant endocrine therapy. Findings expand the clinical utility of BCI (H/I) to a broader range of patients and beyond prognostic risk factors as a predictive endocrine response biomarker for early stage HR+ breast cancer. Research.

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“…High vs Low likelihood of benefit from extended endocrine therapy that is reported separately from the prognostic results (19,21,22).…”

Section: Component Of Bci [Bci (H/i)] Is Based On the H/i Ratio And Pmentioning

confidence: 99%

Section: Component Of Bci [Bci (H/i)] Is Based On the H/i Ratio And Pmentioning

confidence: 99%

Section: Statistical Considerationsmentioning

confidence: 99%

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Breast Cancer Index Predicts Extended Endocrine Benefit to Individualize Selection of Patients with HR+ Early-stage Breast Cancer for 10 Years of Endocrine Therapy

Noordhoek

Treuner

Putter

et al. 2021

Clinical Cancer Research

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“…After demonstrating the effectiveness of an extended endocrine therapy [ 26 ], it became crucial to determine the risk factors for late recurrence in HR-positive breast cancer to guide individualized extended endocrine therapy. Although the optimal predictive factor to select patients who will benefit from extended endocrine therapy remains unclear, it is commonly suggested that the prognostic benefit of extended endocrine therapy can be maximized among patients with a high disease relapse risk [ 27 ]. Based on our results, patients with 25(OH)D deficiency after the 5-year adjuvant endocrine therapy may be considered appropriate candidates for extended endocrine therapy.…”

Section: Discussionmentioning

confidence: 99%

Clinical Implications of Serum 25-Hydroxyvitamin D Status after 5-Year Adjuvant Endocrine Therapy for Late Recurrence of Hormone Receptor-positive Breast Cancer

et al. 2020

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Purpose The prognostic implications of serum vitamin D status after a 5-year adjuvant endocrine therapy on the risk of late recurrence among hormone receptor (HR)-positive breast cancer patients remain unclear. Hence, we investigated this among Korean HR-positive breast cancer patients. Methods A total of 455 patients with HR-positive stage I–III invasive breast cancer who underwent curative surgery at St. Vincent's Hospital between February 2004 and April 2012 were included in this retrospective study. Patients were categorized based on their serum 25-hydroxyvitamin D (25(OH)D) levels after the 5-year adjuvant endocrine therapy. Initial recurrence sites were categorized. The primary clinical outcome was late recurrence-free survival (LRFS). Results Among the 455 patients, 242 and 213 were included in the 25(OH)D-deficient group and 25(OH)D-sufficient group, respectively. Forty-eight patients experienced late recurrence. Across all recurrence sites, the 25(OH)D-deficient group showed significantly worse LRFS rates than the 25(OH)D-sufficient group (hazard ratio [HR], 2.284; 95% confidence interval [CI], 1.155–4.515; p = 0.018). After patient subgrouping based on recurrence site, the 25(OH)D-deficient group also showed significantly worse LRFS rates in terms of regional lymph node (LN) (HR, 17.453; 95% CI, 2.46–128.83; p = 0.005), bone (HR, 2.394; 95% CI, 1.024–5.599; p = 0.044), and visceral (HR, 2.735; 95% CI, 1.182–6.328; p = 0.019) recurrence. However, there was no significant difference between the 2 groups in terms of local recurrence ( p = 0.611). Conclusions We found that 25(OH)D deficiency after the 5-year adjuvant endocrine therapy was associated with worse LRFS among HR-positive breast cancer patients, particularly with respect to regional LN, bone, and visceral recurrence.

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“…Globally, a significant benefit from extended tamoxifen was demonstrated for patients that were classified as BCI (H/I)‐High (HR = 0.35; 95% CI 0.15‐0.86): The risk of recurrence was 27.0% and 37.2% for patients treated with 10‐ and 5‐year tamoxifen, respectively, demonstrating a significant absolute benefit of 10.2% for the reduction in the risk of recurrence. In contrast, there was no significant benefit from an additional 5 years of tamoxifen in patients that were classified as BCI (H/I)‐Low (HR = 1.07; 95% CI 0.69‐1.65) 7 . These results highlight the clinical validity of BCI for the prediction of endocrine response and its clinical utility in tailoring the prescription of extended endocrine therapy.…”

mentioning

confidence: 86%

Extended endocrine therapy in premenopausal breast cancer patients: Where are we now?

Villasco

D’Alonzo

2020

Breast J

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Approximately 25% of new breast cancers are diagnosed in premenopausal patients, 50%‐70% presenting as estrogen receptor‐positive (ER+) breast tumors. Five‐year adjuvant endocrine therapy (ET) with Tamoxifen is the cornerstone treatment for those patients but the evidence that up to 50% of ER + breast cancer distant recurrences develop after this time has now raised some questions. ATLAS and aTTom trials are the only two studies addressing the extension of Tamoxifen beyond 5 years in premenopausal patients. They showed significant DFS and OS benefits at a cost of increased rates of endometrial cancer and pulmonary embolus. Therefore, the selection of the patients at higher recurrence risk and hence deemed to get the most benefit from an extended endocrine therapy has become a major concern. Many clinical and genomic prognostic tools have shown validity in identifying patients at high late recurrence risk, but only the BCI prognostic score was shown to also be predictive of response to extended endocrine therapy. Nevertheless, all the evidence available on extended endocrine therapy in premenopausal patients was derived from trials in which patients were treated with tamoxifen alone and are hardly applicable to the current clinical scenario. In fact, the results of the SOFT and TEXT trials demonstrated the superiority of the addition of ovarian function suppression (OFS) and its association with the aromatase inhibitor (AI) Exemestane to Tamoxifen alone. However, the introduction in the clinical practice of AI + OFS‐based endocrine therapy for the premenopausal patients will very soon lead to an impasse since neither data exist on extended therapy after this treatment schedule nor is there an ongoing trial intended to obtain new evidence.

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Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial

Cited by 146 publications

References 36 publications

Breast Cancer Index Predicts Extended Endocrine Benefit to Individualize Selection of Patients with HR+ Early-stage Breast Cancer for 10 Years of Endocrine Therapy

Breast Cancer Index Predicts Extended Endocrine Benefit to Individualize Selection of Patients with HR+ Early-stage Breast Cancer for 10 Years of Endocrine Therapy

Clinical Implications of Serum 25-Hydroxyvitamin D Status after 5-Year Adjuvant Endocrine Therapy for Late Recurrence of Hormone Receptor-positive Breast Cancer

Extended endocrine therapy in premenopausal breast cancer patients: Where are we now?

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