Accelerated Partial Breast Irradiation: Macrophage Polarisation Shift Classification Identifies High-Risk Tumours in Early Hormone Receptor-Positive Breast Cancer

Studies have demonstrated correlations between accumulations of tumour-associated macrophages (TAMs), especially of M2-like phenotype, and increased mortality in advanced breast cancer. We investigated the prognostic potential of both main macrophage phenotypes in early hormone receptor-positive (HR+) breast cancer. The studied cohort of 136 patients participated in an institutional APBI phase II trial. Patient selection was characterized by HR+, small tumour size and no metastasis. Tissue microarrays from pre-RT resection samples were double stained for CD68/CD163 using immunohistochemistry. CD68+/CD163− cells were considered M1-like macrophages and CD68+/CD163+ was representative of M2-like macrophages. M1 and M2 macrophage densities were analysed semi-automatically in the stromal and intraepithelial tumour compartment. Low M1 and high M2 densities were strongly associated with decreased disease-free survival (DFS). Combined TAM phenotype densities were studied after defining a macrophage shift classification: M1-shifted (M1 high, M2 low) and non-shifted (M1 low, M2 low; M1 high, M2 high) tumours entailed a favourable outcome. In contrast, M2-shifted (M1 low, M2 high) TAM populations were associated with extremely reduced DFS. Thus, the full predictive potential of TAMs was revealed in a combined analysis of both phenotypes. The M2-shifted subgroup of tumours is classified as high-risk and probably not suitable for partial breast irradiation.

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Preliminary results with accelerated partial breast irradiation in high-risk breast cancer patients

Brachytherapy ◽

10.1016/j.brachy.2009.08.011 ◽

2010 ◽

Vol 9 (2) ◽

pp. 171-177 ◽

Cited By ~ 8

Author(s):

Richard B. Wilder ◽

Lisa D. Curcio ◽

Rajesh K. Khanijou ◽

Martin E. Eisner ◽

Jane L. Kakkis ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Patients ◽

Accelerated Partial Breast Irradiation ◽

Partial Breast Irradiation ◽

Breast Irradiation ◽

Breast Cancer Patients ◽

High Risk Breast Cancer ◽

High Risk Breast ◽

Risk Breast Cancer

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Outcomes by breast cancer subtype in patients treated with accelerated partial breast irradiation.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.83 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 83-83

Author(s):

J. B. Wilkinson ◽

C. Shah ◽

M. Amin ◽

S. F. Shaitelman ◽

L. Nadeau ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Subtype ◽

Disease Free Survival ◽

Accelerated Partial Breast Irradiation ◽

Partial Breast Irradiation ◽

Receptor Subtypes ◽

Breast Irradiation ◽

Cancer Subtype ◽

Her 2

83 Background: To determine clinical outcomes for patients treated with accelerated partial breast irradiation (APBI) based on breast cancer subtype. Methods: We evaluated 516 consecutive patients who received APBI with a minimum follow-up of 6 months. Methods of APBI delivery included interstitial brachytherapy (n=221), balloon-based brachytherapy (n=201), and 3D-CRT (n=106). Women were assigned a breast cancer subtype (BCST) based on results of testing for estrogen (ER), progesterone (PR), and human epidermal growth factor (HER2/neu) receptors. Those without test results for all three receptors were excluded. 278 patients were eligible and submitted for analysis. Receptor subtypes were approximated as follows: ER+, PR+/–, and HER-2 negative [luminal A (LA), 164 pts.]; ER+, PR+/–, and HER-2 positive [luminal B (LB), 81 pts.]; ER/PR–, HER-2+ [HER-2 (H2), 5 pts.], and ER/PR/HER-2 negative [basal (B), 28 pts.]. An analysis was then performed to estimate IBTR, RNF, DM, DFS, CSS, and OS. Results: Mean age was 66 years, median follow-up was 4.9 yrs. Basal and H2 subtype patients had higher histologic grades (Gr. 3 = 75% vs. 10% LA/LB, p<0.001), larger tumors (13.0mm vs. 10.7mm LA/LB, p=0.05), and were more likely to receive chemotherapy (68% vs. 15% LA/LB, p<0.001). Basal subtype patients were also more likely to be African American (18% vs. 4% LA/LB, p=0.002). Margin and nodal status were similar between all BCSTs. At five years, IBTR rates were 2.9%, 3.2%, 0%, and 4.8% for LA, LB, H2, and B subtypes, respectively (p=0.75). The IBTR within the B subtype group was due to a single elsewhere failure, the rate of which was not statistically different than that for the LA subtype (2.9%, p=0.30). DM was only seen in LA (2.5%) and LB (1.4%) (p=0.87). Disease-free survival (95-100%), CSS (97%-100%), and OS (80-100%) (Table) were also not statistically different (p=0.98, 0.85, 0.24, respectively) between BCST categories. Conclusions: Five-year local control rates after treatment with APBI are excellent for luminal, HER2, and triple-negative phenotypes of early-stage breast cancer. Further study of BCST is important and may be useful when counseling patients on adjuvant treatment options following breast-conserving surgery.

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Could a Personalized Strategy Using Accelerated Partial Breast Irradiation be an Advantage for Elderly Patients? A Systematic Review of the Literature and Multidisciplinary Opinion

Journal of Oncology ◽

10.1155/2020/3928976 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Luca Tagliaferri ◽

Valentina Lancellotta ◽

Giuseppe Colloca ◽

Fabio Marazzi ◽

Valeria Masiello ◽

...

Keyword(s):

Breast Cancer ◽

Elderly Patients ◽

Disease Free Survival ◽

Accelerated Partial Breast Irradiation ◽

Cochrane Library ◽

Partial Breast Irradiation ◽

Systematic Research ◽

Global Evaluation ◽

Breast Irradiation ◽

Long Term Treatment

Introduction. Elderly patients are underrepresented from a majority of clinical trials and the choice of the best treatment becomes a challenge. The optimal treatment should be personalized and based on a multidisciplinary approach that includes radiation oncologists, surgeons, geriatricians, medical oncologists, social workers, and support services. The global evaluation of the patients and the creation of nomograms may facilitate the definition of long-term treatment benefits minimizing the use of unnecessary therapy. Material and Method. A systematic research using PubMed, Scopus, and Cochrane library was performed to identify full articles analyzing the efficacy of APBI in elderly patients with breast cancer. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results. Seven papers fulfilled the eligibility criteria. The number of evaluated patients was 405 and the median age was 77.7 years. The disease-free survival (DFS) range was 96.1%–100%, the grade 3-4 toxicity range was 0%–6.6%, the cancer-specific survival (CSS) range was 97.9%–100%, and the overall survival (OS) range was 87%–100%. All studies reported excellent/good cosmetic results in a range of 74% to 99%. Conclusion. Accelerated partial breast irradiation (APBI) results in a safe and effective substitute for the adjuvant external beam radiotherapy in selected elderly early-stage breast cancer patients. Based on the relatively low toxicity, APBI should be advised in selected patients with life expectancies larger than 5–10 years.

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Efficacy analysis of high-risk breast cancer patients treated with accelerated partial breast irradiation from a single institution.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.111 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 111-111

Author(s):

P. Y. Chen ◽

F. A. Vicini ◽

C. Mitchell ◽

M. Wallace ◽

P. Benitez ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Patients ◽

Accelerated Partial Breast Irradiation ◽

Partial Breast Irradiation ◽

Breast Irradiation ◽

Breast Cancer Patients ◽

High Risk Breast Cancer ◽

High Risk Breast ◽

Risk Breast Cancer

111 Background: We present the results of an analysis of high-risk breast cancer patients as defined by the NSABP B-39/RTOG 0413 phase III trial, all treated with accelerated partial breast irradiation (APBI) from a single institution. Methods: Between July 1993 and August 2010, 130 patients with any combination of at least one of the high-risk features of estrogen receptor (ER) negativity, age < 50, and/or axillary nodal positivity were treated with 1 of 3 forms of APBI. Sixty-seven patients were treated with interstitial needle-catheter brachytherapy, 44 balloon-based brachytherapy and 19 with 3D conformal external beam radiation therapy. Aside from the high-risk features, general eligibility criteria included infiltrating ductal carcinoma, with inclusion of invasive lobular and DCIS since 2003, margins > 2 mm, and surgically staged axilla. One-hundred eighteen patients had one high-risk factor, 11 had two, and 1 had all three factors. The median tumor size was 12.0 mm with margins > 2 mm in 80% of patients. Greater than 75% had T1 tumors and 50% were ER negative. Thirty-one percent of patients were node positive. Based upon the ASTRO Consensus Guidelines for use of APBI (2009) none of these patients were suitable, 38% cautionary and 62% were unsuitable. Results: Median age was 56.5 yrs (range 40-90). With a median follow-up of 5.3 yrs (0.02-16.9) the 5-yr actuarial local recurrence rate (LR) was 4.2%; regional recurrence (RR) was 2.1%. Median time to LR and RR were 1.2 and 2.8 yrs, respectively. On univariate analysis, the only factor significant for LR was a close/positive margin (p=0.031), as ER/PR, age, nodal status, tumor size, histology, grade, hormonal or chemotherapy were all NS. The 5-yr actuarial cause specific, disease-free, and overall survivals as well as distant metastasis were 94%, 91%, 90%, and 6.4%, respectively. Conclusions: This cohort of NSABP B-39/RTOG 0413 identified high-risk patients who have undergone APBI has yielded local-regional control rates and survival outcomes comparable to standard risk patients undergoing partial breast irradiation. Continued follow-up will be needed to assess the long-term efficacy of such high-risk breast cancer patients treated with APBI.

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Accelerated partial-breast irradiation (APBI) versus whole-breast irradiation (WBI) in treatment of the biological subtypes of breast cancer: An analysis of comparative effectiveness.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.45 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 45-45

Author(s):

Peter Y. Chen ◽

Michelle Wallace ◽

Hong Ye ◽

Jessica Wobb ◽

Maha Saada Jawad ◽

...

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Accelerated Partial Breast Irradiation ◽

Partial Breast Irradiation ◽

Whole Breast Irradiation ◽

Breast Irradiation ◽

Luminal A ◽

Luminal B ◽

Match Pair ◽

Significant Difference

45 Background: To assess if partial vs whole breast irradiation (RT) in treatment of the various biological (bio-) subtypes of breast cancer would lead to differing clinical results, a match pair analysis of APBI vs WBI was undertaken. Methods: Between 3/1993 and 9/2013 all breast CA patients (pts) treated at one institute with either APBI or WBI were matched 1:1 by follow-up (FU) +/- 15 yrs, stage and bio-subtype. This yielded 772 pts of whom 640 were luminal A, 42 luminal B, 58 triple neg (TNBC), 6 HER2+, and 26 triple +. Outcomes were analyzed across the various bio-subtypes for all the pts (APBI + WBI), APBI alone and WBI alone. The endpoints assessed were local recurrence (LR), true recurrence/marginal miss (TR/MM), elsewhere failure (EF), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and contralateral breast failure (CLBF). Results: Mean age was 66 (32-94) with a mean FU of 5.2 years (0.1-18.3). Regarding systemic therapy, 75% received endocrine Rx, while chemotherapy was documented in 21%. For all pts (APBI+WBI) there was no significant difference across the various bio-subtypes with respect to 5, 10 and 15 yr actuarial LR, TR/MM, EF, RR, DM, DFS and CLBF. Likewise, for the 386 APBI-alone treated pts, no significant difference was found between the various bio-subtypes for all the same endpoints reported. However, for the 386 WBI pts, a significant difference was seen in the 15-year actuarial LR between luminal A and TNBC (1.5% vs 7.4%, p = 0.007). Significance was also found in the 15-year actuarial DFS between luminal A/B and TNBC (98.0%, 95.2%; 86.0%, respectively, p = 0.009). Conclusions: In comparing partial to whole breast RT across the various biological subtypes of breast CA, APBI is at least as effective as WBI. However, the retrospective nature of this study along with the limited numbers of pts in the HER2+ and triple + subsets are weaknesses which are acknowledged to exist in this dataset. The addition of further pts in all the biological subtypes, particularly the HER2+ and triple + subsets, along with results from randomized trials incorporating biomarker data will be needed to substantiate these findings.

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A meta-analysis of the efficacy and safety of accelerated partial breast irradiation versus whole-breast irradiation for early-stage breast cancer

Radiation Oncology ◽

10.1186/s13014-021-01752-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Xiaoyong Xiang ◽

Zhen Ding ◽

Lingling Feng ◽

Ning Li

Keyword(s):

Breast Cancer ◽

Local Recurrence ◽

Early Stage ◽

Meta Analysis ◽

Disease Free Survival ◽

Early Stage Breast Cancer ◽

Accelerated Partial Breast Irradiation ◽

Partial Breast Irradiation ◽

Whole Breast Irradiation ◽

Breast Irradiation

Abstract Objective This meta-analysis evaluated the efficacy and safety of accelerated partial breast irradiation versus whole-breast irradiation for early-stage breast cancer after breast-conserving surgery. Materials and methods A systematic search of PubMed, Embase, and the Cochrane libraries was performed according to the PRISMA statement the last 10 years to April 7, 2020 to identify the randomized controlled trials of APBI versus WBI for treating patients with early-stage breast cancer. Two independent observers evaluated the identified studies. The obtained data were analyzed using the RevMan 5.3 software. Results A total of 10 randomized controlled trials involving 15,500 patients with early-stage breast cancer were selected according to the inclusion and exclusion criteria and included in this meta-analysis. In this meta-analysis, we included ten studies that reported local recurrence and found significant differences in local recurrence rates (HR = 1.46; 95% CI 1.20–1.79, P = 0.0002). Further analysis showed that this difference may be related to the choice of treatment methods. No differences in distant metastasis, breast cancer deaths, contralateral breast cancer, disease-free survival, and overall survival rates were observed between WBI and APBI groups. There was no significant difference in late toxicity, cosmetic outcomes and quality of life between the two groups, the compliance and tolerance of the patients were well. Compared to whole breast irradiation, accelerated partial breast irradiation significantly reduced serious (≥ grade 2) early toxicities, especially regarding acute skin toxicity. Conclusions The analysis showed that patients receiving APBI had a higher local recurrence rate, but no differences in distant metastasis, breast cancer deaths, contralateral breast cancer, disease-free survival, and overall survival rates.

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Outcomes After Accelerated Partial Breast Irradiation in Women With Triple Negative Subtype and Other “High Risk” Variables Categorized as Cautionary in The ASTRO Guidelines

Frontiers in Oncology ◽

10.3389/fonc.2021.617439 ◽

2021 ◽

Vol 11 ◽

Author(s):

Anabel Goulding ◽

Lina Asmar ◽

Yunfei Wang ◽

Shannon Tole ◽

Lora Barke ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

High Risk ◽

Triple Negative ◽

Axillary Recurrence ◽

Accelerated Partial Breast Irradiation ◽

Partial Breast Irradiation ◽

Breast Irradiation ◽

Ipsilateral Breast ◽

Risk Patients

PurposeTo report a primary objective clinical outcome of ipsilateral breast recurrence following accelerated partial breast irradiation (APBI) in women with triple negative and other high risk breast cancer (as described in 2017 ASTRO guidelines) (i.e., age 40–49, size 2.1–3.0 cm, estrogen receptor negative and invasive lobular breast cancer). Secondary objectives of axillary and regional failure as well as overall survival are also reported.Methods and MaterialPatients from two clinical trials (NCT01185145, NCT01185132) were treated with 38.5 Gy IMRT or 3D-CRT APBI w/3.85 Gy fraction/BID fractionation for 10 fractions. Triple negative and other high risk patients (n=269) were compared to a total of 478 low risk patients which ASTRO defined as “suitable” for APBI. High risk patients, for the purpose of this study, were defined as those who possess one or more high risk criteria: triple negative (n=30), tumor size >2 cm <3 cm (n=50), HER 2+ (n=54), age range 40–50 years (n=120), ER- (n=43), and ILC histology (n=52).ResultsMedian follow up was 4.0 years for all patients. No significant difference was found for this high-risk cohort at 5 years for ipsilateral breast, or regional recurrences. Axillary recurrence was significantly adversely impacted by triple negative and ER- statuses (p=0.01, p=0.04). There were significant correlations between triple negative type and axillary recurrence on multivariate analysis (p=0.03). Overall survival for all patients was unaffected by any of the high-risk categories.ConclusionThe data from this study suggests that women possessing high risk features are at no more meaningful risk for recurrence than other patients considered to be acceptable for APBI treatment. However, the finding of axillary recurrence in patients with triple negative breast cancer does warrant a degree of caution in proceeding with accelerated partial breast irradiation technique in this patient group.

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Survival outcome and treatment tolerability for postmenopausal females with early stage hormone receptor positive breast cancer treated with different adjuvant hormonal lines (TAM vs. AI vs. switching strategy) for 5 years

QJM ◽

10.1093/qjmed/hcab103.010 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Atef Youssef Riyad ◽

Dalia Abdelghany Elkhodary ◽

Wesam Reda Farag Elghamry ◽

Islam Abdelrahman Kamel Mohamed Zaki

Keyword(s):

Breast Cancer ◽

Aromatase Inhibitor ◽

Early Breast Cancer ◽

Aromatase Inhibitors ◽

Hormone Receptor ◽

Disease Free Survival ◽

Hormonal Treatment ◽

Hormone Receptor Positive ◽

Adjuvant Hormonal Treatment ◽

Her 2

Abstract Background The standard adjuvant endocrine treatment for postmenopausal female patients with hormone receptor positive early breast cancer was 5 years of tamoxifen, but recurrence and side effects restrict its usefulness. The aromatase inhibitor (anastrozole or exemestane or letrozole) was compared with tamoxifen for 5 years or started after completing 2-3 years of tamoxifen in postmenopausal female patients diagnosed with early breast cancer at "Ain Shams University Hospitals" Objective The aim of the study was to measure survival outcome and treatment tolerability for postmenopausal females with Hormone Receptor Positive early breast cancer who received adjuvant hormonal treatment with tamoxifen [TAM] only for 5 years versus those who received adjuvant hormonal treatment with tamoxifen [TAM] for 2 years switching to aromatase inhibitors [AI] in the sequential 3 years versus those who received adjuvant hormonal treatment with aromatase inhibitors [AI] solely for 5 years. Patients and methods This study included 100 postmenopausal women with early breast cancer who presented at the Clinical Oncology Department, Ain Shams University, in the interval from January 2010 until December 2015. Conclusion Similar disease free survival and overall survival were observed among the three studied groups. Switching tamoxifen to aromatase inhibitors provides better tolerability in terms of endometrial thickness when compared to 5 years of tamoxifen monotherapy. Patients who administer aromatase inhibitor included in the switching strategy experience less osteoporosis and less generalized bone pain compared to upfront aromatase inhibitor to 5 years. There was a significant improvement of disease free survival (DFS) in human epidermal growth factor receptor 2 (HER 2) negative patients receiving any adjuvant hormonal treatment line for five years in comparison to HER 2 positive patients receiving the same adjuvant hormonal treatment for five years.

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Five-day accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) in stage 0-II breast cancer: A report of 214 cases with up to 39 month follow-up.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12508 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12508-e12508

Author(s):

Rufus J. Mark ◽

Valerie Gorman ◽

Michal Wolski ◽

Steven McCullough

Keyword(s):

Breast Cancer ◽

Intensity Modulated Radiation Therapy ◽

Target Volume ◽

Accelerated Partial Breast Irradiation ◽

Partial Breast Irradiation ◽

Breast Irradiation ◽

Skin Reactions ◽

Cosmetic Results ◽

Non Invasive

e12508 Background: Randomized trials in stage 0-II breast cancer have proven that APBI given via HDR implant in 5 days is equivalent to whole breast irradiation (WBI) given in 5-6 weeks in regard to breast tumor local recurrence (LR). However, complications have been significant. Recently APBI using non-invasive IMRT given in 5 fractions has been shown in another randomized trial with 10 year follow-up to be equivalent to WBI in 6 weeks, with respect to LR. IMRT was superior in regard to acute effects, late effects, and cosmesis. In the randomized clinical trial of APBI IMRT, the Clinical Target Volume (CTV) was defined by the injection of individual fiducial markers bordering the surgical cavity. We have used the Biozorb fiducial system to localize the CTV for IMRT. We sought to confirm the APBI IMRT results with this simpler less labor intensive fiducial placement system. Methods: Between 2017 and 2021, 214 patients have undergone IMRT targeted to a Biozorb defined CTV with the walls of the surgical cavity sewn to the Biozorb device. Eligible patients were older than age 40, had tumor sizes < 3 cm, negative surgical margins, and negative sentinel node dissections. IMRT dose was 30 Gy given in 5 fractions. Dose Constraints were as follows : V-30 Gy < 105%, Ipsilateral Breast V-15 Gy < 50%, Ipsilateral Lung V-10 Gy < 20%, Contralateral Lung V-5 Gy < 10%, Heart V-3 Gy < 20%, Contralateral Breast Dmax < 2 Gy and Skin Dmax < 27 Gy. The Planning Target Volume (PTV) ranged from 27 to 355 cc with a median of 80 cc. PTV = CTV + 1-2 cm. Results: Follow-up ranged from 1-39 months with a median of 20 months. LR has been 0% (0/214). There have been no skin reactions or seromas. Infection has occurred in one patient (0.5%). Four (1.9%) patients developed pain around the Biozorb site. This resolved on a short courses of steroids in all cases. Cosmetic results as rated by the Surgeon, Radiation Oncologist, and Nurse, were rated excellent in 99.0% (212/214) of cases. Conclusions: Non-invasive APBI with IMRT given qd over 5 days targeted to Biozorb has resulted in LR, complications, and cosmetic results which compare favorably to invasive APBI given bid with HDR implant. At last follow-up, there have been no LR, skin reactions, or significant complications. Cosmesis has been excellent in 99.0% of patients.

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Advances in Adjuvant Endocrine Therapy for Postmenopausal Women

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.0946 ◽

2008 ◽

Vol 26 (5) ◽

pp. 798-805 ◽

Cited By ~ 74

Author(s):

Nancy U. Lin ◽

Eric P. Winer

Keyword(s):

Breast Cancer ◽

Postmenopausal Women ◽

Endocrine Therapy ◽

Hormone Receptor ◽

Disease Free Survival ◽

Breast Cancer Diagnosis ◽

Endocrine Treatment ◽

Future Research ◽

Sequential Approach ◽

Hormone Receptor Positive

Hormone receptor-positive cancers are the most common tumor subtype among postmenopausal women with breast cancer. Despite substantial improvements in disease-free survival and overall survival with tamoxifen and chemotherapy, recurrences still occur, and may ultimately lead to death from breast cancer. Importantly, disease recurrence includes both early and late events, with over half of all recurrences detected more than 5 years from initial breast cancer diagnosis. In recent years, a number of large, randomized trials have evaluated the role of the aromatase inhibitors (AIs) in postmenopausal women with hormone receptor-positive breast cancer. These studies have tested one of three approaches: (1) an upfront AI, (2) a sequential approach after 2-3 years of tamoxifen, and (3) extended endocrine therapy beyond 5 years. Results of these studies have challenged the previous standard of a 5-year course of tamoxifen alone. While the AIs have become a standard component of treatment for most postmenopausal women, many questions remain as to how best tailor endocrine treatment to individual patients. In addition, despite the gains achieved with the AIs, many recurrences are not prevented, and novel strategies are urgently needed, particularly for those women at high risk of recurrence. In this article, we review the efficacy and toxicity data from the available trials of endocrine therapy in the postmenopausal setting. We outline controversies in choosing the optimal endocrine approach, and we discuss selected ongoing studies. Finally, we highlight future research directions, such as the need to understand host and tumor heterogeneity.

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