Estrogen Receptor-positive Early Breast Cancer Research Articles

The clinical usefulness of the CTS5 in the prediction of late distant recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

BackgroundClinical Treatment Score post-5 years (CTS5) is a promising prognostic tool to evaluate late distant recurrence (DR) risk for breast cancer after 5-year adjuvant endocrine therapy.Patients and methodsAmong 560 postmenopausal women with pathological stage I–III estrogen receptor-positive (ER+) primary breast cancer, 383 women who had received 5-year adjuvant endocrine therapy without any recurrence at 5 years after surgery were included in this study. The CTS5 was calculated for each patient using a previously published formula, and the patients were stratified by their CTS5 values into the low-, intermediate- and high-CTS5 risk groups.ResultsAccording to the CTS5, 205 (53.5%), 106 (27.7%) and 72 (18.8%) patients were classified into the low-, intermediate-, and high-CTS5 risk groups, respectively. A higher ER expression level was significantly associated with the low CTS5. The increased administration of adjuvant chemotherapy was significantly associated with a high CTS5. The occurrence of DR was higher in the intermediate and high CTS5 groups than in the low CTS5 group. The DRFS in the low CTS5 risk group was significantly better than that in the intermediate- or high-risk groups. In the ER-high or HER2-negative (HER2−) group, the DRFS in the low-risk group was significantly better than that of the intermediate- or high-risk groups. However, in the low-ER or HER2-positive group, there was no significant difference in DRFS among the three risk groups.ConclusionsIn postmenopausal women with ER+ breast cancer, low CTS5 was considered to be associated with a very low risk of late DR. Thus, extended endocrine therapy may be unnecessary for patients with low CTS5 scores. Extended endocrine therapy should be offered for patients with intermediate or high CTS5 scores, especially those with high-ER and HER2− breast cancer.

Gene Expression Assay in the Management of Early Breast Cancer.

The addition of adjuvant chemotherapy to hormonal therapy is often considered questionable in patients with estrogen receptor-positive early breast cancer. Low risk of disease relapse after endocrine treatment alone and/or a low sensitivity to chemotherapy are reasons behind not all patients benefit from chemotherapy. Most of the patients could be exposed to unnecessary treatment- related adverse events and health care costs when treatment decision-making is based only on classical clinical histological features. Gene expression profile has been developed to refine physician's decision-making process and to tailor personalized treatment to patients. In particular, these tests are designed to spare patients the side effects of unnecessary treatment, and ensure that adjuvant chemotherapy is correctly recommended to patients with early breast cancer. In this review, we will discuss the main diagnostic tests and their potential clinical applications (Oncotype DX, MammaPrint, PAM50/Prosigna, EndoPredict, MapQuant Dx, IHC4, and Theros-Breast Cancer Gene Expression Ratio Assay).

Willingness of women with early estrogen receptor-positive breast cancer to take adjuvant CDK4/6 inhibitors.

The steady decline in breast cancer (bca) mortality has come at the cost of increasingly toxic and expensive adjuvant therapies. Trials evaluating the addition of 2 or 3 years of cyclin-dependent kinase 4/6 (cdk4/6) inhibitors to adjuvant endocrine therapy (et) are ongoing, but the willingness of patients to take such additional therapy is unknown. We surveyed 100 consecutive postmenopausal women with nonmetastatic estrogen receptor-positive bca who had initiated adjuvant et within the preceding 2 years. Participants were asked about perceived recurrence risk, bca worry, and overall health. They were then asked about their willingness to accept 2 years of treatment with an additional oral drug that would reduce recurrence by 40% for a range of baseline recurrence risks in 2 hypothetical scenarios. Mean age of the 99 evaluable participants was 61.7 years. In the scenario with no drug toxicity, 85% of respondents were likely to accept the new drug for a reduction in recurrence to 30% from 50%, but only 49% would take the drug if risk was reduced to 3% from 5%. In a scenario with drug-induced fatigue, the corresponding drug acceptance rates were 55% and 39% respectively. For the second scenario, bca worry was correlated with increased willingness to take the drug, even for only a 2% absolute reduction in recurrence risk. The willingness of patients with estrogen receptor-positive bca to take an adjuvant cdk4/6 inhibitor will greatly depend on the expected benefit and toxicities described to them as well as on worry about bca recurrence.

Response to neoadjuvant chemotherapy and the 21-gene breast recurrence score in young women with estrogen receptor-positive early breast cancer.

514 Background: The 21- gene Breast Recurrence Score predicts benefit from adjuvant chemotherapy in estrogen receptor positive (ER+), HER-2 negative (-) breast cancer (BC). We aimed to examine whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NAC). Methods: We identified patients with stage I-III ER+/HER2− BC treated with NAC from the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤ 40 years. The 21-gene assay was performed on tumor specimens removed prior to NAC either as part of clinical care or retrospectively for research. Pathologic complete response (pCR) was defined as no residual invasive tumor (ypT0/is ypN0). The relationship between Recurrence Score result (RS) and pCR was evaluated using logistic regression modeling. Results: 76 women in the cohort had undergone NAC for ER+, HER2- BC and were eligible for this analysis: 5 had undergone clinical 21-gene assay testing, 71 had banked specimens retrospectively tested. Median age at diagnosis was 36.7 (24.3-40). Most tumors were of ductal histology (78%), high grade (51%), progesterone receptor (PgR) positive (86%), ≥T2 (88%), clinically node positive (74%), and anthracycline and taxane containing protocols were administered in 86% of cases. RS ranged between 5-75 with 50% > 25 and only 4 < 11. Mean RS was significantly higher among tumors achieving pCR vs. non-pCR response (51.9 vs. 26.6, pwilcoxon= 0.0005). pCR rate in patients with RS > 25 was 21% (8/38) vs. 5% in patients with RS < 25 (2/38), with both pCRs in the <25 group in patients with RS 21-25. In univariable analysis, PgR negativity (odds ratio (OR) 5.62, 95% confidence interval (CI) 1.27-24.89, p = 0.02), high grade (OR 9.03, 95%CI 1.07-76.32, p = 0.04) and higher RS as a continuous variable (OR 1.08, 95%CI 1.04-1.13, p = 0.0003) were associated with a greater likelihood of pCR. In multivariable analysis only RS remained significantly associated with pCR (OR: 1.07, 95%CI 1.01-1.12, p = 0.01): a 7% increase in the odds of pCR for every 1-point increase in RS. Conclusions: In young women with ER+, HER2- BC who received NAC, higher pretreatment RS was associated with an increased likelihood of pCR. Genomic expression profiling assays may have a role in decision-making in young women in need of neoadjuvant therapy. For women with low likelihood of benefiting from NAC, alternative approaches are clearly warranted. Given the demonstrated efficacy of neoadjuvant endocrine therapy in post-menopausal women, further evaluation in young women should be pursued.

Tumour-infiltrating lymphocytes and response to neoadjuvant letrozole in patients with early oestrogen receptor-positive breast cancer: analysis from a nationwide phase II DBCG trial

BackgroundThe presence of tumour-infiltrating lymphocytes (TILs) is associated with response to neoadjuvant chemotherapy among patients with triple-negative and HER2-positive breast cancer. However, the significance of TILs is less clear in luminal breast cancer. Here, we in postmenopausal patients with primary oestrogen receptor-positive (ER+), HER2 normal, operable breast cancer assessed the importance of inducing TILs during 4 months of letrozole on response in a neoadjuvant phase II study.MethodsParticipants were postmenopausal women with ER+, HER2 normal operable breast cancer assigned to 4 months of neoadjuvant letrozole. Pretreatment core biopsies and surgical specimens were assessed centrally for the percentage of TILs on haematoxylin and eosin-stained slides according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines. Pathological response was assessed by the Residual Cancer Burden (RCB) index and a modified Miller-Payne grading system and was analysed according to change in TILs.ResultsTumour specimens were available from 106 of the 112 patients treated per protocol. TIL concentration increased with mean 6.8 percentage point (p < 0.0001) during treatment (range − 39 to 60). An increase in TILs was significantly associated with pathological response with OR = 0.71 (95% CI 0.53–0.96; p = 0.02) per 10% absolute increase for pathological response and correspondingly OR = 0.56 (95% CI 0.40–0.78; p = 0.0007) for lower RCB index per 10% increase.ConclusionIncreasing TILs during letrozole was significantly associated with a poor treatment response. An increase in TILs during endocrine therapy might imply immunogenicity, and these patients could be targetable by immunotherapy.Trial registrationClinicalTrials.govNCT00908531, registered 27 May 2009.

Abstract P5-06-20: Usefulness of CTS5 for the prediction of late distant recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

Abstract &amp;lt;Background&amp;gt; The Clinical Treatment Score post-5 years (CTS5) is a prognostic tool to estimate the residual risk of distant recurrence (DR) after 5 years of endocrine therapy in postmenopausal women with estrogen receptor (ER)-positive breast cancer. (J Clin Oncol, 2018; 19: 1941-1947). CTS5 might be useful to decide the indication of extended adjuvant endocrine therapy after 5years. &amp;lt;Purpose&amp;gt; This study was conducted to elucidate the usefulness of CTS5 for the prediction of late DR in postmenopausal women with ER-positive early breast cancer treated in our department. &amp;lt;Patients and Methods&amp;gt; CTS5 was calculated in 377 postmenopausal patients with ER-positive breast cancer who underwent surgery between 2003 and 2009. They had received 5-year adjuvant endocrine therapy without DR. CTS5 is stratified into three groups; low, intermediate and high risk of DR. The relationships between CTS5 and the clinicopathological characteristics and prognosis were evaluated. &amp;lt;Results&amp;gt; According to CTS5, 202 (53.6%), 104 (27.6%) and 71 (18.8%) patients were divided into low, intermediate and high-risk of late DR groups. In the CTS5-high risk group, significantly more positive lymph nodes (p&amp;lt;0.0001), larger tumor size (p&amp;lt;0.0001), higher histological grade (p&amp;lt;0.0001), more administration of adjuvant chemotherapy (p&amp;lt;0.0001), more administration of adjuvant endocrine therapy of Aromatase inhibitor (AI) (p=0.0029), more visceral distant metastasis (p=0.0029), lower ER expression (p=0.0064) were observed. Significantly lower incidence of DR was observed in CTS5-low risk group. Thus, CTS5 was significantly prognostic for late DR. Intriguingly, in the CTS5-low risk group, administration of endocrine therapy of AI (p=0.0023), lower histological grade (HG1, 2; p=0.0011), ER high expression (TS; 6-8 p=0.0002), and positive PgR (p=0.0007) were significantly better DR-free survival (DRFS). &amp;lt;Conclusion&amp;gt; CTS5 demonstrated clinical validity for predicting late DR in this study cohort. IN the CTS5-low risk group, the incidence of late DR was significantly lower than that of in CTS5-intermediate or high risk group. The low CTS5 might be useful to decide the indication of 5-year adjuvant endocrine therapy in the postmenopausal patients with ER-positive early breast cancer. Citation Format: Wakako Tajiri, Azusa Sugii, Hideki Ijichi, Hiroki Ueo, Chinami Koga, Yoshiaki Nakamura, Masahiro Okamoto, Kennichi Taguchi, Eriko Tokunaga. Usefulness of CTS5 for the prediction of late distant recurrence in postmenopausal women with estrogen receptor-positive early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-20.

Progress in endocrine therapy for early breast cancer

Breast cancer is a malignant tumor that occurs in the epithelial tissues of the breast gland. The cause of the disease is not fully understood and may be related to genetic, endocrine and other factors. For estrogen or progesterone receptor-positive early breast cancer, endocrine therapy is efficient, simple, and fewer side-effect, so endocrine therapy plays an important role in the treatment for early breast cancer. But most of them will develop drug-resistant after 8 to 14 months and have to combine with chemotherapy or molecule targeted therapy. However, there are still different ideas in the effects of endocrine therapy drugs alone or in combination with chemotherapy or molecule targeted drugs, pre-menopausally or post-menopausally.

Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: position statement summary.

Representatives appointed by relevant Australian medical societies used a systematic approach for adaptation of guidelines (ADAPTE) to formulate clinical consensus recommendations on assessment and management of bone health in women with oestrogen receptor-positive early breast cancer receiving endocrine therapy. The current evidence suggests that women receiving adjuvant aromatase inhibitors and pre-menopausal woman treated with tamoxifen have accelerated bone loss and that women receiving adjuvant aromatase inhibitors have increased fracture risk. Both bisphosphonates and denosumab prevent bone loss; additionally, denosumab has proven anti-fracture benefit in post-menopausal women receiving aromatase inhibitors for hormone receptor-positive breast cancer. Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density measurement, with monitoring based on risk factors. Weight-bearing exercise and vitamin D and calcium sufficiency are recommended routinely. Anti-resorptive treatment is indicated in women with prevalent or incident clinical or morphometric fragility fractures, and should be considered in women with a T score (or Z score in women aged <50 years) of <-2.0 at any site, or if annual bone loss is ≥5%, considering baseline bone mineral density and other fracture risk factors. Duration of anti-resorptive treatment can be individualised based on absolute fracture risk. Relative to their skeletal benefits, risks of adverse events with anti-resorptive treatments are low. Skeletal health should be considered in the decision-making process regarding choice and duration of endocrine therapy. Before and during endocrine therapy, skeletal health should be assessed regularly, optimised by non-pharmacological intervention and, where indicated, anti-resorptive treatment, in an individualised, multidisciplinary approach.

Cardiometabolic Effects of Endocrine Treatment of Estrogen Receptor-Positive Early Breast Cancer.

Estrogen receptor–positive early breast cancer is common and has a relatively good prognosis. It shares risk factors with cardiovascular disease, and cardiovascular disease is an important competing cause of mortality. Adjuvant endocrine therapy with aromatase inhibitors (requiring concomitant ovarian suppression in premenopausal women) or selective estrogen receptor modulators (usually tamoxifen) exert oncologic benefits by respectively inhibiting estradiol synthesis or breast estrogen receptor signaling. Aromatase inhibitors cause systemic estradiol depletion. Tamoxifen has mixed agonistic/antagonistic effects in a tissue-dependent fashion. Given that estrogens modulate cardiometabolic risk, a review of the effects of endocrine therapy on cardiometabolic outcomes is pertinent. The current, but limited, evidence suggests that tamoxifen treatment, although associated with increases in body fat, hepatic steatosis, serum triglycerides, and diabetes risk, modestly reduces low-density lipoprotein cholesterol and lipoprotein(a) and may have favorable effects on markers of subclinical atherosclerosis. Tamoxifen is associated with either no effect on, or a reduction in, cardiovascular events, and it is associated with an increase in venous thromboembolic events. Aromatase inhibitors, although fewer studies are available and often confounded by comparison with tamoxifen, have not been consistently associated with adverse changes in cardiometabolic risk factors or increases in cardiovascular events. Further clinical trials designed to evaluate cardiometabolic outcomes are needed to more accurately determine the effects of endocrine therapy on cardiovascular risks, to inform individualized decisions regarding choice and duration of endocrine therapy, and to implement evidence-based strategies to mitigate cardiometabolic risks. In the meantime, although breast cancer–specific evidence for benefit of lifestyle measures is available and recommended routinely, proactive monitoring and treatment of cardiovascular risk factors should follow general population recommendations.

P009 - Usefulness of CTS5 for the prediction of late distant recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

P009 - Usefulness of CTS5 for the prediction of late distant recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

Multi-gene assays: effect on chemotherapy use, toxicity and cost in estrogen receptor-positive early stage breast cancer.

To assess multi-gene assay (MGA) effects on chemotherapy use, toxicities, recurrences, and costs in estrogen receptor-positive early breast cancer. Meta-analysis performed using data from public databases.Results: Studies included 12,202 women. Relative to no testing, chemotherapy use was higher with 12-gene and 70-gene and lower with PAM50 (commercial) and 21-gene MGAs. Overall, 1643 distant recurrences occurred with no testing, declining by 231 (21-gene), 121 (70-gene), 54 (12-gene) and 94 (PAM50); only the 21-gene assay resulted in no risk of increasing the number of distant recurrences. Relative to 'no testing', total cost of care declined only with 21-gene MGA. MGAs differ in chemotherapy use and related outcomes for women with estrogen receptor-positive early breast cancer.

Impact of ovarian function suppression in premenopausal women with estrogen receptor-positive early breast cancer.

This manuscript aims at providing an updated overview on the role of adding ovarian function suppression to tamoxifen or an aromatase inhibitor as adjuvant endocrine therapy in premenopausal women with estrogen receptor-positive early breast cancer. Until recently, tamoxifen alone was the only recommended adjuvant treatment option for premenopausal women with estrogen receptor-positive disease. However, recent important evidence has contributed to significantly modify the endocrine treatment landscape in this setting. With the only exception of patients with low-risk clinical-pathological features characterized by excellent survival outcomes with tamoxifen alone, the use of ovarian function suppression is to be considered standard of care for most of premenopausal women with estrogen receptor-positive disease. Regarding the choice of its best partner as endocrine agent, the available data suggest that the higher the risk of disease recurrence the larger benefit can be observed with a more profound estrogen deprivation that can be obtained with ovarian function suppression and an aromatase inhibitor as compared to ovarian function suppression and tamoxifen. Despite the significant improvement in our understanding on the role of ovarian function suppression in this setting, several unanswered questions remain and further research efforts are needed in the field.

Risk stratification in early breast cancer in premenopausal and postmenopausal women: integrating genomic assays with clinicopathological features.

There is growing consensus that genomic assays provide useful complementary information to clinicopathological features in oestrogen receptor-positive breast cancers. Here, ongoing research with multigene tests used for postmenopausal breast cancer and new emerging prognostic and predictive markers for pre and postmenopausal women are summarised. Results of the TAILORx trial have shown that women with an intermediate risk score do not benefit from adjuvant chemotherapy. Prosgina has been further investigated in a contemporary patient population in postmenopausal women and its use has been extended for premenopausal women. The EndoPredict was extensively used in decision-impact studies showing that its use can potentially reduce the need for adjuvant chemotherapy. Several new genomic assays have been developed, with some of them showing promising use for women with early oestrogen receptor-positive breast cancer. New areas of research for prediction of recurrence and risk stratification involve the development of immune gene signatures that carry modest but significant prognostic value. The recent expansion of high-throughput technology platforms including circulating tumour DNA/RNA and microRNA offer new opportunities to improve prediction models, particularly in women with oestrogen receptor-negative disease and premenopausal women. Genomic assays have clearly improved prognostication of early oestrogen receptor-positive breast cancer but it is clear that standard clinicopathological parameters are still very important when identifying patient for adjuvant chemotherapy.

Prognostic Value of the Detection of Lymphovascular Invasion in Hormone Receptor-Positive Early Breast Cancer in the Era of Molecular Profiling

Background: Lymphovascular invasion (LVI) is considered a negative prognostic factor in early breast cancer, but its role in decision-making regarding adjuvant chemotherapy is unclear in the current era of molecular profiling. This study sought to evaluate the association of LVI status with the recurrence score (RS) on the multigene Oncotype DX (ODX) assay and its impact on outcome. Methods: Patients with early estrogen receptor-positive breast cancer who underwent ODX analysis in 2005–2012 were retrospectively identified. Clinical data were collected from the medical records. The Cox proportional-hazards ratio was used to determine recurrence rates. The prognostic significance of LVI was evaluated by competing risks analysis. Results: LVI was detected in 38 of 657 patients (6%). LVI was not associated with ODX RS (p = 0.225). However, it was significantly associated with other known prognostic factors and with worse 5-year disease-free survival (HR 2.93; 95% CI 1.02–8.39; p = 0.04). Overall survival (OS) analysis according to the ODX subgroups showed that the presence of LVI was associated with worse 5-year OS (p = 0.04) only in the intermediate-risk group, while LVI had no effect on the low- or high-risk groups. Conclusions: Although LVI was not significantly associated with a higher ODX RS, it may infer a worse outcome, especially in ODX intermediate-risk patients.

Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer

BackgroundSeveral prognostic signatures for early oestrogen receptor-positive (ER+) breast cancer have been established with a 10-year follow-up. We tested the hypothesis that signatures optimised for 0–5-year and 5–10-year follow-up separately are more prognostic than a single signature optimised for 10 years.MethodsGenes previously identified as prognostic or associated with endocrine resistance were tested in publicly available microarray data set using Cox regression of 747 ER+/HER2− samples from post-menopausal patients treated with 5 years of endocrine therapy. RNA expression of the selected genes was assayed in primary ER+/HER2− tumours from 948 post-menopausal patients treated with 5 years of anastrozole or tamoxifen in the TransATAC cohort. Prognostic signatures for 0–10, 0–5 and 5–10 years were derived using a penalised Cox regression (elastic net). Signature comparison was performed with likelihood ratio statistics. Validation was done by a case-control (POLAR) study in 422 samples derived from a cohort of 1449.ResultsNinety-three genes were selected by the modelling of microarray data; 63 of these were significantly prognostic in TransATAC, most similarly across each time period. Contrary to our hypothesis, the derived early and late signatures were not significantly more prognostic than the 18-gene 10-year signature. The 18-gene 10-year signature was internally validated in the TransATAC validation set, showing prognostic information similar to that of Oncotype DX Recurrence Score, PAM50 risk of recurrence score, Breast Cancer Index and IHC4 (score based on four IHC markers), as well as in the external POLAR case-control set.ConclusionsThe derived 10-year signature predicts risk of metastasis in patients with ER+/HER2− breast cancer similar to commercial signatures. The hypothesis that early and late prognostic signatures are significantly more informative than a single signature was rejected.

Effectiveness of bisphosphonate combined with activated vitamin D in patients with aromatase inhibitor-induced osteoporosis after breast cancer operation

ObjectivesWe compared the effectiveness of bisphosphonates combined with activated vitamin D administered for therapy of aromatase inhibitor-induced osteoporosis after a breast cancer operation and primary postmenopausal osteoporosis through propensity score matching. MethodsForty-eight postmenopausal patients with estrogen receptor-positive early breast cancer, who had postoperative adjuvant treatment with aromatase inhibitors and whose T-score of bone mineral density (BMD) decreased below −2.5 (AI group), and 48 patients of primary postmenopausal osteoporosis (PO group) enrolled in this retrospective observational study. They were administered monthly risedronate or minodronate, and daily alfacalcitol or eldecalcitol were combined. Their BMD (L2–4, L-BMD), serum-corrected calcium, serum phosphate, tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase (BAP), estimated glomerular filtration rate, urine calcium/creatinine ratio, intact-parathyroid hormone, and 25-hydroxy vitamin D were measured before treatment and until 24 months. ResultsL-BMD values increased with time compared with the baseline values in each group, and there was no significant difference in the groups. Percentage value of TRACP-5b decreased rapidly after 6 months and maintained low level until 24 months in both groups. Percentage value of BAP in the AI group decreased continuously until 24 months. In contrast, the percentage change in the PO group plateaued after 6 months. ConclusionsIt is suggested that monthly oral bisphosphonate combined with activated Vitamin D is an effective therapy to increase BMD in the aromatase inhibitor-induced osteoporosis after breast cancer operation. Monitoring of kidney function and concentration of Ca in blood and urine may be necessary.

The Warwick Experience of the Oncotype DX® Breast Recurrence Score® Assay as a Predictor of Chemotherapy Administration

Introduction: Oncotype DX® analyses the expression of 21 genes within tumour tissue to determine a Recurrence Score® (RS). RS is a marker of risk for distant recurrence in oestrogen receptor-positive early breast cancer, allowing patient-specific benefit of chemotherapy to be evaluated. Our aim was to determine whether the introduction of Oncotype DX led to a net reduction in chemotherapy use. Methods: Consecutive patients that underwent Oncotype DX at Warwick Hospital were reviewed. Patients were anonymised and re-discussed at a multidisciplinary team meeting (MDM; without RS), and treatment recommendations were recorded. This was compared to the original MDM outcome (recommendations made with RS). Differences were analysed using Wilcoxon signed-rank test. Results: 67 patients were identified. Proportions of high, intermediate and low risk were 28, 33 and 39% (n = 19/22/26), respectively. Without RS, 56 (84%) patients were recommended for chemotherapy and 3 were not. The remaining 8 patients were deemed borderline for requiring chemotherapy and referred for discussion with an oncologist. With availability of RS, 34 (50%) patients were recommended for chemotherapy, and 24 (43%) patients were spared chemotherapy (p < 0.0005). The net reduction in chemotherapy was 33%. Conclusion: There has been a significant reduction in chemotherapy usage in patients at Warwick since the introduction of Oncotype DX.

Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australasian Menopause Society and the Clinical Oncology Society of Australia.

To formulate clinical consensus recommendations on bone health assessment and management of women with oestrogen receptor-positive early breast cancer receiving endocrine therapy, representatives appointed by relevant Australian Medical Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing 5 key questions. Women receiving adjuvant aromatase inhibitors and the subset of premenopausal woman treated with tamoxifen have accelerated bone loss and increased fracture risk. Both bisphosphonates and denosumab prevent bone loss; additionally, denosumab has proven antifracture benefit. Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density (BMD) measurement, with monitoring based on risk factors. Weight-bearing exercise, vitamin D and calcium sufficiency are recommended routinely. Antiresorptive treatment should be considered in women with prevalent or incident clinical or morphometric fractures, a T-score (or Z-scores in women <50years) of <-2.0 at any site, or if annual bone loss is ≥5%, considering baseline BMD and other fracture risk factors. Duration of antiresorptive treatment can be individualized based on absolute fracture risk. Relative to their skeletal benefits, risks of adverse events with antiresorptive treatments are low. Skeletal health should be considered in the decision-making process regarding choice and duration of endocrine therapy. Before and during endocrine therapy, skeletal health should be assessed regularly, optimized by nonpharmacological intervention and where indicated antiresorptive treatment, in an individualized, multidisciplinary approach. Clinical trials are needed to better delineate long-term fracture risks of adjuvant endocrine therapy and to determine the efficacy of interventions designed to minimize these risks.

Applying new Magee equations for predicting the Oncotype Dx recurrence score.

Breast cancer is one of the most prevalent cancers in women. Oncotype Dx is a multi-gene assay frequently used to predict the recurrence risk for estrogen receptor-positive early breast cancer, with values < 18 considered low risk; ≥ 18 and ≤ 30, intermediate risk; and > 30, high risk. Patients at a high risk for recurrence are more likely to benefit from chemotherapy treatment. In this study, clinicopathological parameters for 37 cases of early breast cancer with available Oncotype Dx results were used to estimate the recurrence score using the three new Magee equations. Correlation studies with Oncotype Dx results were performed. Applying the same cutoff points as Oncotype Dx, patients were categorized into low-, intermediate- and high-risk groups according to their estimated recurrence scores. Pearson correlation coefficient (R) values between estimated and actual recurrence score were 0.73, 0.66, and 0.70 for Magee equations 1, 2 and 3, respectively. The concordance values between actual and estimated recurrence scores were 57.6%, 52.9%, and 57.6% for Magee equations 1, 2 and 3, respectively. Using standard pathologic measures and immunohistochemistry scores in these three linear Magee equations, most low and high recurrence risk cases can be predicted with a strong positive correlation coefficient, high concordance and negligible two-step discordance. Magee equations are user-friendly and can be used to predict the recurrence score in early breast cancer cases.

Omitting radiotherapy in women ≥ 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe

PurposeThe aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET). Patients and MethodsEligibility criteria were: consecutive patients with age ≥65 years, BCS + sentinel node biopsy, clear margins, unifocal T1N0M0 breast cancer tumor, Elston-Ellis histological grade 1 or 2 and estrogen receptor-positive tumor. After informed consent, adjuvant ET for 5 years was prescribed. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer and overall survival. ResultsBetween 2006 and 2012, 603 women were included from 14 Swedish centers. Median age was 71.1 years (range 65–90). After a median follow-up of 68 months 16 IBTR (cumulative incidence at five-year follow-up; 1.2%, 95% CI, 0.6% to 2.5%), 6 regional recurrences (one combined with IBTR), 2 distant recurrences (both without IBTR or regional recurrence) and 13 contralateral breast cancers were observed. There were 48 deaths. One death (2.1%) was due to breast cancer and 13 (27.1%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.0% (95% CI, 90.5% to 94.9%). ConclusionBCS and ET without RT seem to be a safe treatment option in women ≥ 65 years with early breast cancer and favorable histopathology. The risk of IBTR is comparable to the risk of contralateral breast cancer. Moreover, concurrent morbidity dominates over breast cancer as leading cause of death in this cohort with low-risk breast tumors.