Low-risk Early Breast Cancer Research Articles

Can Ki-67 serve as a suitable marker to indicate the necessity of staging diagnostics in cases of low-risk breast cancer?

For many years, staging tests have not been routinely employed for low-risk early breast cancer (EBC). However, the role of Ki-67 in determining the need for staging tests in low-risk EBC remains unclear. Our study aimed to assess the number and types of staging diagnostics, additional imaging, false-positive results, and rate of distant metastases in low-risk EBC with low and high Ki-67 (< / ≥ 25%). This is a retrospective, single institution cohort study. All patients with newly diagnosed low-risk breast cancer at the University Medical Center in Freiburg in 2017 and 2021 were included. Low-risk was defined as clinical tumor stage T1/2, node negative (N0), hormone receptor positive, HER2 negative, asymptomatic EBC. Information on demographics, clinical and pathological characteristics, as well as number and type of performed staging diagnostics was obtained. Rate and type of additional imaging or follow-up diagnostics due to suspicious findings was analyzed. The patients were divided into two groups (Ki-67 < and ≥ 25%) and rates of distant metastases, performed staging diagnostics and false positive rates were compared. A total of 189 patients with low-risk EBC were identified, with 54% (n = 102) having Ki-67 < 25% and 46% (n = 87) having Ki-67 ≥ 25%. Risk for distant metastases was 0% in Ki-67 < 25% and 1.1% in patients with Ki-67 ≥ 25% (p = 0.46). Due to suspicious findings in the initial staging diagnostic, additional imaging was required for 11.8% (n = 12) of patients with Ki-67 < 25% compared to 19.5% (n = 17) of patients with Ki-67 ≥ 25% (p = 0.16). False positive rates did not differ significantly between the two groups (7.6% in Ki-67 < 25% vs. 9.8% in Ki-67 ≥ 25%; p = 0.55). Distant metastases are rare in low-risk EBC. All in all, staging diagnostics should not be routinely employed in this patient population. Only patients with high Ki-67 developed distant metastases. In these cases, staging diagnostics may be discussed with the patient.

Ten-Year Results of Accelerated Partial-Breast Irradiation with Interstitial Multicatheter Brachytherapy after Breast-Conserving Surgery for Low-Risk Early Breast Cancer.

Patients with an early carcinoma of the breast are commonly treated by breast-conserving surgery (BCS) and postoperative radiotherapy. Partial-breast irradiation has gained acceptance in the last few years. Between December 2008 and December 2017, 182 low-risk breast cancer patients treated by BCS in the four university hospitals of the province of Las Palmas and treated with APBI using interstitial multicatheter brachytherapy were included in this study. After a mean follow-up for survivors of 10 years, the treatment was shown to be safe, as no severe acute/late toxicity (grade ≥ 3) was observed. The 10-year IBTR was 1.7% (95%CI: 0.7-2.7%), and the cause-specific survival was 94.9% (95%CI: 93.2-96.6%). We suggest that multicatheter brachytherapy after BCS is safe and effective in early breast cancer patients.

Omission of radiation therapy post breast conserving surgery

Radiation therapy (RT) after breast conserving surgery decreases the risks of local recurrence and breast cancer mortality in the multidisciplinary management of patients with breast cancer. However, breast cancer is a heterogeneous disease, and the absolute benefit of post-operative RT in individual patients varies substantially.Clinical trials aiming to identify patients with low-risk early breast cancer in whom post-operative RT may be safely omitted, based on conventional clinical-pathologic variables alone, have not provided sufficiently tailored information on local recurrence risk assessment to guide treatment decisions. The majority of patients with early breast cancer continue to be routinely treated with RT after breast conserving surgery. This approach may represent over-treatment for a substantial proportion of the patients.The clinical impact of genomic signatures on local therapy decisions for early breast cancer has been remarkably modest due to the lack of high-level evidence supporting their clinical validity for assessment of the risk of local recurrence. Efforts to personalise breast cancer care must be supported by high level evidence to enable balanced, informed treatment decisions. These considerations underpin the importance of ongoing biomarker-directed clinical trials to generate the high-level evidence necessary for setting the future standard of care in personalised local therapy for patients with early breast cancer.

Diagnostic performance of additional imaging tests for staging purposes in a bicentric German series of low-risk early breast cancer patients

PurposeLow-risk early breast cancer rarely leads to the development of metastatic disease, and in these patients, additional imaging test is controversial. The aim of our study was to evaluate the conventional staging procedures in a bicentric German series of low-risk breast carcinoma patients.MethodsRetrospective evaluation of all patients diagnosed with early, low-risk breast cancer at Saarland University Hospital and Freiburg University Hospital in 2017 was performed. Clinical patient characteristics, the number and type of additional imaging examinations, follow-up examinations, and results were evaluated. The detection rate of metastases and the rate of false-positive findings were analyzed.ResultsA total of 203 patients were included, with all patients received at least one additional imaging test. Initially, a total of 562 additional imaging examinations were performed: 166 chest X-rays, 169 upper abdominal ultrasounds, 199 bone scans, 27 computer tomographies (CT) chest and abdomen, and 1 CT abdomen. 6.8% of patients had abnormal findings reported, requiring 38 additional imaging examinations. One patient (0.5%) was found to have bone metastases. The rate of false-positive findings in the performed additional imaging procedures was 6.6%.ConclusionMetastatic disease was detected in one of 203 patients with low-risk early breast cancer. A total of 562 examinations and additional 38 follow-up examinations were performed without detection of metastasis (this corresponds to approximately 3 examinations/patient). The rate of false-positive findings was 6.6%. The performance of additional imaging procedures for detection of distant metastases should be critically reconsidered in patients with low-risk early breast cancer.

Physicians' Opinion on Intraoperative Radiotherapy as a Therapeutic De-Escalation Option in Older Women with Early Breast Cancer.

Intraoperative radiotherapy (IORT) is a therapeutic de-escalation option in older women with low-risk early breast cancer (EBC). A qualitative study was implemented to describe EBC physicians' points of view on IORT as a de-escalation option. Recorded face-to-face and telephone semi-structured interviews were conducted among diverse physicians from seven French comprehensive cancer centers. Interview transcripts were grouped as corpus to construct a typology. Thematic analysis was performed. Positions toward IORT were contrasted between the 16 participating physicians. Five fully supported IORT as a de-escalation option, four were not in favor, and seven had a more reserved or neutral opinion. Points of divergence concerned treatment efficacy, treatment duration, side effects and sequelae, psychological impact, compliance with adjuvant endocrine therapy, logistical constraints, financial cost, and availability of other techniques of partial breast irradiation. Physicians in favor of IORT emphasized direct benefits for the patient, and those against pointed the lack of specific guidelines, risk of lost opportunity in older women with long life expectancy, and challenges of shared decision making. Despite national policies to preserve cancer patients' quality of life and increase their participation in medical decision making, therapeutic de-escalation using IORT is not consensual among physicians. Further efforts are needed to promote patient-centered care.

Rationale and design of a phase II trial of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for N0/N1mi, HER2\u2009+\u2009early breast cancer (PHAEDRA)

BackgroundThe de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated.MethodsThis is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1–7, then 4 mg bid on days 8–21) or the first 2 cycles (4 mg tid on days 1–7, then 4 mg bid on days 8–42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea.DiscussionThis is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea.Trial registrationClinicalTrials.gov Identifier: NCT04659499. Registered on December 9, 2020.

Abstract OT1-12-07: A phase 2 study of chemotherapy de-escalation using a pathological response-guided strategy in patients with HER2-positive, low-risk early breast cancer: PHERGain-2

Abstract Background: The introduction of trastuzumab (H) and pertuzumab (P) and ado-trastuzumab emtansine (T-DM1) has drastically improved clinical outcomes in patients (pts) with HER2-positive early breast cancer, allowing to explore chemotherapy-sparing approaches in this population. PHERGain trial is evaluating the efficacy of dual HER2-blockade with HP as both neoadjuvant and adjuvant treatment using an 18F-fluorodeoxyglucose-PET-based and a pathological response-adapted strategy [Pérez-García JM et al., Lancet Oncol. 2021;22:858-871]. PHERGain-2 study is an additional step forward and aims to assess the feasibility of chemotherapy de-escalation with neoadjuvant HP followed by adjuvant HP or T-DM1 using a pathological response-adapted strategy in low-risk HER2-positive early breast cancer pts. Trial Design: PHERGain-2 is a multicenter, open-label, non-comparative, phase 2 trial. Eligible participants are patients aged ≥18 years with previously untreated, centrally confirmed, HER2-positive (immunohistochemical score 3+), invasive, node-negative breast cancer (&amp;gt;0.5 and &amp;lt;2.5 cm in tumor size). Eastern Cooperative Oncology Group performance status of 0 or 1, left ventricular ejection fraction of at least 55%, and adequate organ function are also required. Pts will receive the fixed-dose combination of HP for subcutaneous injection (1200 mg P plus 600 mg H loading dose, followed by 600 mg P plus 600 mg H maintenance doses) administered every 3 weeks for 8 cycles as neoadjuvant treatment. Hormone receptor-positive pts will be additionally given letrozole (2.5 mg/day orally) if postmenopausal or tamoxifen (20 mg/day orally) plus gonadotropin-releasing hormone analogue if pre-/peri-menopausal or men. Centrally reviewed MRI will be performed at screening and within 2 weeks prior to surgery. Surgery will be done within 4 weeks after the last dose of study treatment. After surgery, pts who achieve a pathologic complete response in breast and axilla (ypT0/is, ypN0) will continue HP for a total of 18 cycles; pts with residual invasive breast disease and/or ypN0(i+/mol+), ypN1mi will receive T-DM1 for 10 cycles; and pts with ypN1-3 will receive T-DM1 for 10 cycles and, at investigator’s discretion, chemotherapy before starting T-DM1. Adjuvant endocrine therapy and radiotherapy will be administered as per hormone receptor status and institutional practices. The primary efficacy and safety endpoints are 3-year recurrence-free interval (RFI) as per STEEP criteria and patient-reported outcomes after 1 year from neoadjuvant treatment initiation as measured by the EORTC-QLQ-C30 scale in the overall population. Key secondary endpoints include pathologic complete response, residual cancer burden, breast-conserving surgery rate; 3-year and 5-year event-free survival, relapse-free survival, distant relapse-free survival, disease-free survival, invasive disease-free survival, breast cancer-specific survival, overall survival; and safety and tolerability as per CTCAE 5.0. A total of 393 pts will be enrolled. The sample size was calculated with the log-minus-log Kaplan-Meier method. The analysis will test the null hypothesis that the 3-year RFI rate is ≤94% and the alternative hypothesis that 3-year RFI rate is ≥98%. With the expectation a 20% dropout rate, a sample size of 393 pts is necessary to attain 80% power at nominal level of two-sided alpha of 0.05. The analysis for the primary efficacy and safety endpoints will be conducted with 95% confidence intervals based on Kaplan-Meier estimator. This trial was opened to accrual in May 2021. Citation Format: José Manuel Pérez-García, Ángel Guerrero-Zotano, Jacques Medioni, Andreas Schneeweiss, Marco Colleoni, Miguel Sampayo-Cordero, Andrea Malfettone, Javier Cortés, Antonio Llombart-Cussac. A phase 2 study of chemotherapy de-escalation using a pathological response-guided strategy in patients with HER2-positive, low-risk early breast cancer: PHERGain-2 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-12-07.

Abstract PD7-04: Avoidance of radiotherapy for low risk early breast cancer using LUMINA Trial criteria and accounting for endocrine therapy adherence

Abstract Objectives: Adjuvant radiotherapy (RT) is a standard component of breast conserving therapy for early stage breast cancer. However, in especially low risk disease, the benefit of radiotherapy may be small. Randomized trials have investigated the feasibility of RT omission in subgroups of patients defined by clinicopathologic variables only. Five biomarker based single arm trials (IDEA, PRECISION, LUMINA, PRIMETIME, EXPERT trials) are ongoing with the goal of using molecular data to refine patient selection for RT omission. This analysis reports on the treatment outcomes of low risk ER positive early stage breast cancer treated with adjuvant RT or RT omission at a multi-hospital health system. Inclusion criteria from LUMINA trial were used to select a very low risk population and subgroup analyses were performed to investigate the influence of endocrine therapy (ET) adherence on outcomes. Methods: The shared electronic health record of multiple facilities within a university health system was queried to identify women with pathologic T1-2 N0 breast cancer treated with breast-conserving surgery between 2007 and 2016. Data collection included demographic features, tumor characteristics, treatment type, endocrine therapy adherence, and locoregional recurrence events. Analysis was restricted to those patients treated with EBRT or RT omission. To identify the low risk patients, inclusion and exclusion criteria from LUMINA trial (age ≥ 55, unifocal, unilateral, ductal, tubular or mucinous histology, T1N0, grade 1-2, ER+ and PR&amp;gt;20 and HER2-, LVI -, margin &amp;gt; 2mm, Ki67 ≤ 13.25, agreed to start endocrine therapy) were applied. Five-year loco-regional control (LRC) rates were compared across groups using the Kaplan-Meier method. Results: 115 patients met LUMINA inclusion criteria. Of these, 84 were treated with EBRT and 31 with RT omission. ET adherence information were available for 101 patients. Patients who completed 5 years of ET or discontinued owing to disease recurrence or death were categorized as ET adherent (ETA) and those who discontinued before 5 years due to other reasons were categorized as ET non-adherent (ETNA). Median ET duration in ETA was 60 months (49-118 months) and in ETNA was 19 months (1-58 months). 5-year LRC rates for RT vs. RT omission were 100 % vs. 94 % (95% CI 82-100). This difference was borderline statistically significant (p = 0.06). On subset analysis, 5-year LRC rates for RT and RT omission were both 100 % in ETA. The 5-year LRC rates for RT vs. RT omission were 100 % vs. 83% (95% CI 54-100) in ETNA (p= 0.18). Conclusion: In this modern series, patients with very low risk early breast cancer selected using criteria from the LUMINA trial exhibited excellent local control with ET alone if they were treatment adherent. This finding awaits validation in large prospective cohorts. By contrast, ET alone may be insufficient in patients likely to be non-adherent to treatment. Notably, prospective trials should closely follow and report ET adherence. Table 1.Patient tumor and treatment characteristicsEBRT (n=84)RT omission (n=31)Age (median)63 (55-76)73 (63-81)Median follow-up (months)53 (8-98)43 (7-70)HistologyDuctal72 (86%)30 (97%)Other12 (14%)1 (3%)StageT1mic2 (2%)0T1a12 (14%)9 (29%)T1b34 (41%)11 (35%)T1c36(43%)11 (35%)GradeG149 (58%)23 (74%)G235 (42%)8 (26%)Endocrine therapy (ET)ET median duration (months)60 (2-118)55 (1-72)ET Adherent60 (71%)17 (55%)ET Non-adherent15 (18%)9 (29%)ET adherence not available9 (11%)5 (16%) Table 2.5-year Loco-regional control ratesRTRT omissionLog-rank test p valueLUMINA All (N=115)100%94%0.06LUMINA ET Adherent (N=77)100%100%LUMINA ET Non-adherent (N=24)100%83%0.18 Citation Format: Seung Won Seol, Lauren Weller, Travis Pflederer, Chelain Goodman, Eric D Donnelly, John P Hayes, Jonathan B Strauss. Avoidance of radiotherapy for low risk early breast cancer using LUMINA Trial criteria and accounting for endocrine therapy adherence [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-04.

PH-0222 Irradiation With or Without Boost in Low Risk Early Breast Cancer: Data from a Large Health System

PH-0222 Irradiation With or Without Boost in Low Risk Early Breast Cancer: Data from a Large Health System

Abstract PS6-38: A comparison of oncotype DX and NHS predict to assess the benefit of adjuvant chemotherapy in patients with early breast cancer

Abstract INTRODUCTION Early breast cancer (EBC) which is hormone receptor positive, HER2 negative and 0-3 Lymph node positive, defines a Luminal subtype with an excellent outcome and the benefit of adjuvant chemotherapy in this subgroup of patients is increasingly questioned. Gene-expression profile tests have evolved to help stratify risk and to individualise treatment decisions. The 21-gene recurrence-score assay, “Oncotype DX” (ODX) is a genomic test used to quantify the likelihood of distant recurrence (Recurrence Score i.e. RS) and predict chemotherapy benefit. Although it is included in international guidelines as a tool to identify patients who could safely avoid adjuvant chemotherapy, its utility is restricted due to cost in countries with limited resources where it is not covered by insurance. The “NHS Predict” (NHSP) is a freely available online prognostic and predictive test based on cancer registry data. It utilises an algorithm based on clinical parameters and biomarker status to provide an estimate of survival as well as the potential benefit of third generation chemotherapy, hormonal and targeted therapy. The NHSP is based on “Clinical Risk (CR)” while the ODX is based on “Genomic Risk (GR)” assessment. The present study was undertaken to compare the results obtained by ODX with those obtained by NHSP so as to determine the concordance of the two tests and establish the utility of the NHSP in resource-constrained countries. PATIENTS AND METHODS Patients with early ER positive, HER2 negative, 0-3 nodes positive breast cancer, who underwent the ODX assay from January 2010 to March 2020 at a tertiary referral centre were entered into this study. Patients were stratified as per the ODX RS into Low (RS= 0-20 for ≤ 50 years, 0-25 for &amp;gt;50 years) and High (RS= &amp;gt;21 for ≤ 50 years and 26-100 for &amp;gt;50 years) risk for recurrence with absolute chemotherapy benefit (ACB) estimated to be ≤7% and &amp;gt;7% respectively at 9 years.Subsequently, the NHS Predict 2.2 tool (https://breast.predict.nhs.uk/tool ) was used to compute the absolute benefit of third generation chemotherapy for each of these patients. Relevant clinical data i.e. age, menopausal status, tumour size, grade, Ki-67, ER/PR/HER2 status, nodal status and method of detection was entered into the algorithm. The ACB at 10 years, as determined by NHSP, was stratified into Low risk≤ 7% and High risk &amp;gt;7% so as to correspond to the ACB derived from ODX. The results obtained by NHSP were compared to those of the ODX to determine the concordance between the two tests. RESULTS 104 patients were entered into the study. The mean age was 53 years (range 31-76 years), 39.4% were premenopausal and 60.5% post-menopausal. The average tumour size was 19.4mm (range 8-55mm) with 61.53% T1, 36.53% T2 and 1.92% with T3 disease.14.4% were grade 1, 66.3% grade 2, and 19.2% grade 3. 74% were lymph node negative and 14.4%, 9.6% and 0.96% had 1, 2 and 3 positive nodes respectively. On ODX evaluation, low RS was seen in 87 (83.65%), and high RS in 17(16.34%) patients. As per NHSP, 99 (95.19%) patients were classified into low CR and 5 (4.8%) into high CR. There was 82.7% (86/104) concordance between NHSP and ODX with discordance in 18 patients. Of the concordant group, 84 had low CR and GR and 2 had high CR and GR. In the discordant group 15 patients had low CR on NHSP but high GR on ODX and while 3 patients had a high CR on NHSP but ODX showed low GR. CONCLUSIONS In a group of patients with low clinical risk EBC there is high concordance between the NHSP and ODX tests. There is a subgroup of patients with discordant results in whom the ODX may identify patients who could potentially benefit with adjuvant chemotherapy. NHSP can aid decision making regarding adjuvant chemotherapy and identify patients who could potentially avoid chemotherapy in low risk early breast cancer. Citation Format: Vinay Deshmane, Anuja Raniwala. A comparison of oncotype DX and NHS predict to assess the benefit of adjuvant chemotherapy in patients with early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-38.

Choosing Wisely – Implication based on Indian data in our patients with breast cancer (INR vs. USD)

Objectives: Breast cancer is increasing in India due to aging population, better awareness among general public, willingness to seek treatment of cancers, and easier access to cancers centers. We present our single-center data over a 2-year period and discuss cost implications taking the example of metronomic chemotherapy maintenance and predictive markers in early breast cancer. Material and Methods: Prospectively collected data of all consecutive patients with breast cancer registered between September 2017 and August 2019 were evaluated. Clinical features, stage, receptor status, and other features were tabulated. Statistical analysis was using SAS version 9.4 – Chi-square test and Fisher’s exact test were performed. P ≤ 0.05 was considered as statistically significant. Results: For the 484 consecutive patients, the median age was 50 years. This included EBC (201, 42%), LABC (141, 29%), and MBC (142, 29%). ER expression was seen in 52% of cases (253/484), PR in 47% (229/484), and Her2 was positive in 47% (229/484). Finally, 83 patients (17%) were identified as TNBC. HR-positive Her2-negative EBC constituted 111/484 patients (23%). Discussion: If our 83 TNBC patients were given metronomic maintenance chemotherapy, their 3-year overall survival (OS) is projected to increase from 54% to 100% at a cost of INR 8191/- per patient (equivalent to USD 109/-). If our 111 HR-positive Her2-negative EBC patients were evaluated for risk by biomarker test validated in Indian patients, 76 of these would be spared the toxicity of adjuvant CT. This would also result in saving on the cost of chemotherapy medication of INR 4,035,296/- in India (equivalent to USD 53,699/- if treated in USD). In addition, they would also have better quality of life (QoL). Conclusion: It is possible to identify patients with low risk early breast cancer using Can assist and save them from unnecessary cost and/or toxicity.

Long-Term MINDACT Results Affirm Excellent Prognosis for Clinically and Genetically Low-Risk Early Breast Cancer.

The 8-year distant metastasis-free survival rate is 94.7% for patients with clinically and genetically low-risk early breast cancer who forgo adjuvant chemotherapy, according to updated findings from the phase III MINDACT trial.

Adjuvant breast radiotherapy, endocrine therapy, or both after breast conserving surgery in older women with low-risk breast cancer: Results from a population-based study

Background and PurposeThe relative benefit of adjuvant radiotherapy (RT) alone in older women with low-risk early breast cancer (EBC) remains unclear. It is hypothesized that adjuvant RT-alone can improve outcomes of older patients with low-risk EBC, similar to endocrine therapy (ET) alone or combination of RT + ET. MethodsIn this population based study, we identified all women aged ≥70 with T1–2, N0, ER+ve, Her-2/neu−ve EBC treated with breast conserving surgery (BCS), followed by adjuvant treatments (RT-alone, ET-alone, or RT + ET combination) from 2005 to 2015. Primary outcome measures were recurrence-free survival (RFS), overall survival (OS), and breast cancer specific survival (BCSS). Treatment details were collected and Charlson Comorbidity Index (CCI) was calculated. ResultsA total of 1166 patients were identified. Median follow-up was 76.5 months. Adjuvant treatments: BCS only 130 (11%), RT 378 (32.5%), ET 161 (14%), and RT + ET 497 (42.5%). Less than 60% of women completed 5-years of ET. Compared to BCS alone, RT resulted in significant improvement in RFS (HR = 0.174; p < 0.001), similar to ET (HR = 0.414; p = 0.007) and RT + ET (HR = 0.236; p < 0.001). Determinants of OS were age, tumor grade, comorbidities, and adjuvant therapy. Increased comorbidity scores (0 vs. 1; 0 vs. ≥2) were associated with reduced OS (HR = 1.40; p = 0.013 and HR = 1.98; p < 0.001), without impact on RFS or BCSS. ConclusionsAdjuvant RT-alone is a reasonable alternative to ET or RT + ET for older women with biologically favorable EBC. No difference in RFS or BCSS was noted between RT, ET, and RT + ET. Comorbidity was independently associated with reduced overall survival.

A Food and Drug Administration analysis of survival outcomes comparing the Adjuvant Paclitaxel and Trastuzumab trial with an external control from historical clinical trials.

Although the Adjuvant Paclitaxel and Trastuzumab (APT) trial has been adopted clinically, single-arm trials have limitations, and interest remains whether these patients with small node-negative human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) would benefit from more intensive chemotherapy. This analysis explored whether external controls can contextualize single-arm studies to add to clinical decision making in the use of de-escalated therapy in patients with low-risk HER2-positive EBC. Patient-level data from five randomized trials supporting drug approval in adjuvant HER2-positive EBC were pooled, and patients with low-risk EBC were selected (n= 1770). Patients treated concurrently with trastuzumab and either anthracycline/cyclophosphamide/taxane/trastuzumab (ACTH) or taxane/carboplatin/trastuzumab (TCH; n= 1366) were matched (1:1) to patients treated with paclitaxel and trastuzumab (TH) in the APT trial (n= 406) using propensity scores. Patients treated with anthracycline/cyclophosphamide/taxane (ACT; n=374) were also matched (1:1) to those treated with TH. Propensity scores were estimated using covariates of age, tumor stage, estrogen receptor status, progesterone receptor status, and histological grade. After matching, the estimated probabilities of invasive disease-free survival (iDFS) at 3 and 5 years were 98.6% and 96.5% in the TH arm, and 96.6% and 92.9% in the ACTH/TCH arm, respectively. The estimated probabilities of overall survival (OS) at 3 and 5 years were 99.7% and 99.3% in the TH arm, and 99.0% and 97.4% in the ACTH/TCH arm, respectively. Comparing the TH arm with the ACT arm in the matched sample, the estimated difference in iDFS was 7.5% (TH 98.8% and ACT 91.3%) at 3 years and 12.6% (TH 96.1% and ACT 83.5%) at 5 years. The estimated difference in OS was 2.6% (TH 100% and ACT 97.4%) at 3 years, and 5.3% (TH 99.3% and ACT 94.0%) at 5 years. Our analyses suggest that patients' outcomes in both arms were in general similar, thus providing additional reassurance regarding de-escalation of therapy.

Fatigue following radiotherapy of low-risk early breast cancer \u2013 a randomized controlled trial of intraoperative electron radiotherapy versus standard hypofractionated whole-breast radiotherapy: the COSMOPOLITAN trial (NCT03838419)

BackgroundFatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients.MethodsThis trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size < 2,5 cm, ER pos. Her2neu neg., age > 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale.DiscussionThe present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance.Trial registrationThe study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. “Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)”.Study statusOngoing study. Start of recruitment was December 2019.

Effect of adjuvant radiotherapy in elderly patients with breast cancer.

Radiotherapy (RT) is of critical importance in the locoregional management of early breast cancer. Although RT is routinely used following breast conserving surgery (BCS), patients may occasionally be effectively treated with BCS alone. Currently, the selection of patients undergoing BCS who do not need breast irradiation is under investigation. With the advancement of personalized medicine, there is an increasing interest in reduction of aggressive treatments especially in older women. The primary objective of this study was to identify elderly patients who may forego breast irradiation after BCS without measurable consequences on local tumor growth and survival. We analyzed 2384 early breast cancer patients aged 70 and older who were treated in 17 German certified breast cancer centers between 2001 and 2009. We compared RT versus no RT after guideline adherent (GA) BCS. The outcomes studied were breast cancer recurrence (RFS) and breast cancer-specific survival (BCSS). Low-risk patients were defined by luminal A, tumor size T1 or T2 and node-negative whereas higher-risk patients were defined by patients with G3 or T3/T4 or node-positive or other than Luminal A tumors. To test if there is a difference between two or more survival curves, we used the Gp family of tests of Harrington and Fleming. The median age was 77 yrs (mean 77.6±5.6 y) and the median observation time 46 mths (mean 48.9±24.8 mths). 950 (39.8%) patients were low-risk and 1434 (60.2%) were higher-risk. 1298 (54.4%) patients received GA BCS of which 85.0% (1103) received GA-RT and only 15% (195) did not. For low-risk patients with GA-BCS there were no significant differences in RFS (log rank p = 0.651) and in BCSS (p = 0.573) stratified by GA-RT. 5 years RFS in both groups were > 97%. For higher-risk patients with GA-BCS we found a significant difference (p<0.001) in RFS and tumor-associated OS stratified by GA-RT. The results remain the same after adjusting by adjuvant systemic treatment (AST) and comorbidity (ASA and NYHA). Patients aged 70 years and older suffering from low-risk early breast cancer with GA-BCS can avoid breast irradiation with <3% chance of relapse. In the case of higher-risk, breast irradiation should be used routinely following GA-BCS. As a side effect of these results, removing the entire breast of elderly low risk patients to spare them from breast irradiation seems to be not necessary.

First Experience in Korea of Stereotactic Partial Breast Irradiation for Low-Risk Early-Stage Breast Cancer

Purpose: Accelerated partial breast irradiation (A-PBI) in Korean women has been considered impracticable, owing to small breast volume and lack of high-precision radiotherapy experience. We present the first experience of stereotactic-PBI (S-PBI) with CyberKnife M6 to investigate feasibility of use and early toxicities in Korean women with early breast cancers.Materials and Methods: A total of 104 breasts receiving S-PBI at our institution between September 2017 and October 2018 were reviewed. Patients were selected based on the American Society for Radiation Oncology (ASTRO), American Brachytherapy Society, American Society of Breast Surgeons, and Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology guidelines. A dose of 30 Gy in 5 fractions (NCT01162200) was used. Gold fiducials were routinely inserted near the tumor bed for tracking. Constraints regarding organs-at-risk followed the NSABP-B39/RTOG 0413 protocol.Results: Median follow-up was for 13 months. Patients were categorized as “suitable” (71.2%) or “cautionary” (28.8%) according to 2017 the ASTRO guidelines. No tracking failure of inserted gold fiducials occurred. Median planning target volume (PTV) and PTV-to-whole breast volume ratio was 73.6 mL (interquartile range, 58.8–103.9 mL) and 17.0% (13.3–19.1%), respectively. Median PTV V95%, PTV Dmax, and ipsilateral breast V50% were 97.8% (96.2–98.8%), 105.3% (104.2–106.4%), and 35.5% (28.3–39.8%), respectively. No immediate post-S-PBI toxicity ≥ grade 2 was reported, except grade 2 induration in three breasts. All patients remain disease-free to date.Conclusion: The first use of S-PBI in Korean women was feasible and safe for selected early breast cancer. Based on these results, we have initiated a prospective study (NCT03568981) to test S-PBI in whole-breast irradiation for low-risk early breast cancer.

Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer

Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008–December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3–1.9) and 98.3% (95% CI 97.3–99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.

Adjuvant radiotherapy for low-risk early breast cancer in elderly women: evidence from randomized trials.

Breast cancer is the most common cancer pathology in women in the Western world. The median age at diagnosis is 60 years and in the coming decades it is estimated that the number of elderly women affected reaches an important percentage. This aging of the cancer population, associated with its inherent comorbidities and aggravated by the lack of consensus about the most appropriate treatment, make it difficult to administer an effective postoperative treatment in elderly women with a low-risk profile. An exhaustive geriatric evaluation is a sine qua non condition to opt for a specific type of treatment. To date, several options are available such as endocrine therapy (ET) alone, moderate/high hypofractionation and various accelerated partial breast irradiation (APBI) techniques. In this article, we provide information about each of them.

Radiation Therapy Without Hormone Therapy for Women Age 70 or Above with Low-Risk Early Breast Cancer: A Microsimulation

Hormone therapy without radiation therapy is considered appropriate for women age 70 or above with low-risk, hormone-positive breast cancer after partial mastectomy. However, some patients may prefer radiation without hormone therapy, for which there is minimal modern data. We modeled the comparative efficacy of aromatase inhibition alone without radiation versus radiation alone without hormone therapy. We constructed a patient-level Markov model and compared 5 years of anastrozole to a 15-fraction course of radiation without boost or anastrozole. The relative effectiveness between treatments was based on the National Surgical Adjuvant Breast and Bowel Project B-21 trial, which was further adjusted such that the endocrine-alone arm matched the Cancer and Leukemia Group B 9343 and PRIME II trials. Common or severe side effects were considered. Eight survival metrics were assessed and validated against clinical trial data. The cost-efficacy of each strategy was considered using the quality-adjusted life year and incremental cost-effectiveness ratio (ICER). The model's predicted outcomes matched those demonstrated by modern trials. Aromatase inhibitors were superior in preventing contralateral cancers, with a small impact on the risk of distant metastatic disease. Radiation was superior in preventing ipsilateral breast tumor recurrence with a small impact on regional failure. No clinically significant differences were seen in the other 4 oncologic endpoints. Differences in quality-adjusted life years were small, but radiation therapy was $3809 more expensive over the average lifetime. The ICER suggested anastrozole was cost-effective in 62% of probabilistic simulations. However, the ICER was unstable owing to a denominator that approached zero. Women age 70 or above with low-risk early breast cancer who are reluctant or unable to pursue adjuvant aromatase inhibition can safely pursue adjuvant radiation alone with limited differences in outcome and a modest increase in costs.