Research on the cutoff tumor size of omitting radiotherapy for BCSS after breast conserving surgery in women aged 65 years or oder with low-risk invasive breast carcinoma: Results based on the SEER database

BackgroundRadiotherapy after breast-conserving surgery (BCS) is not always necessary in older women staged T1N0M0 with low-risk invasive breast cancer, but few studies have concluded the detailed tumor size as a reference for avoiding radiotherapy. The study was conducted to explore and identify the optimal cutoff tumor size.MethodsThe study population was from the Surveillance, Epidemiology, and End Results (SEER) database in 2010–2016. Propensity score matching was used to balance the confounders between groups. Predictors associated with survival were analyzed by Kaplan–Meier, X-tile, Cox proportional hazards model and competing risk model.ResultsA total of 52049 women and 3846 deaths were included in the cohort with a median follow-up of 34 months. Based on the cutoff value determined by X-tile analysis, the study population were divided into small tumor group (≤14 mm in diameter) and large tumor group (>14 mm in diameter). Small tumors and radiotherapy were correlated with better breast cancer-specific survival (BCSS). In subgroup analysis, the absolute benefit of BCSS in 6 years attributed to radiotherapy was only 0.90% (RT vs. non- RT:98.77% vs. 97.87%) for patients with small tumors but up to 3.33% (RT vs. non- RT:97.10% vs. 93.77%) for those with large tumors.ConclusionSmall tumors and adjuvant radiotherapy were associated with improved long-term prognosis, and 14 mm in diameter was the cutoff tumor size of omitting radiotherapy for patients aged 65 or older with T1N0M0 stage, ER+ and HER2-breast carcinoma after BCS.     

Omitting radiation therapy in women with triple-negative breast cancer leads to worse breast cancer-specific survival

PurposeTo examine locoregional recurrence (LRR) and breast cancer-specific survival (BCSS) after breast-conserving therapy (BCT) or mastectomy (ME) with or without radiation therapy (RT) in triple-negative breast cancer (TNBC).Material & MethodsWe identified non-metastatic TNBC cases from a single institution database. BCT, ME with RT (ME + RT) and ME only were compared with respect to LRR and BCSS. Cox regression models were used to analyze the association between prognostic factors and outcome.Results439 patients fulfilled the inclusion criteria. Median follow-up was 10.2 years (interquartile range 7.9; 12.4 years). Patients in the BCT (n = 239), ME + RT (n = 116) and ME only (n = 84) group differed with respect to age, pT, pN, lymphovascular invasion, lymph node dissection and chemotherapy administration. Ten-year LRR rates were seven percent, three percent and eight percent for the BCT, ME + RT and ME only group, respectively. pN was associated with LRR. In multivariable analysis LRR were significantly lower in the ME + RT group compared to the BCT and the ME only group (p 0.037 and 0.020, respectively).Ten year BCSS was 87%, 84% and 75% for the BCT, ME + RT and ME only group, respectively. pT, pN, lymph node dissection, lymphovascular invasion and the administration of chemotherapy were associated with BCSS. In multivariable analysis BCSS was significantly lower in the ME only group compared to the BCT group and the ME + RT group (p 0.047 and 0.003, respectively).ConclusionTNBC patients treated with ME without adjuvant RT showed significant lower BCSS compared to patients treated with BCT or ME + RT and significant more LRR compared to ME + RT when corrected for known clinicopathological prognostic factors.     

An evaluation of the impact of technical bias on the concordance rate between primary and recurrent tumors in breast cancer

PurposeWhether or not to biopsy the metastasis in recurrent breast cancer has become mired in controversy. Several studies have shown an important discordance of the immunohistochemical (IHC) determinations for ER, PR and HER2 between primary (PT) and recurrent tumors (RT). Yet it remains unknown within this what impact technical issues have. The aim of our study was to assess whether technical variability might have an impact on the concordance between PT and RT.MethodsIHC determinations in paired biopsies from PT and RT were compared under routine vs study conditions. In the former, pathological analysis reproduced the conditions used in the routine of a University Pathology Department. In the latter, in a technical bias-minimizing manner, samples were re-assessed at the same timing and by two independent observers.Results128 paired biopsies from 64 patients were analyzed under both conditions. Concordance under routine vs study conditions for ER was 66% vs 93.4% (p = 0.001), for PR 58.7% vs 80.3% (p = 0.064) and for HER2 86.8% vs 96.8% (p = 0.25). Kappa index under routine versus study conditions for ER was 0.27 vs 0.79 (p = 0.002), for PR 0.26 vs 0.39 (p = 0.47) and for HER2 0.67 vs 0.9 (p = 0.14).ConclusionsAlthough discordance rate between PT and RT decreased under conditions minimizing technical issues, some discordant cases appeared not to be subjected to this confounding factor. Either for clinical practice or for future studies reassessment of PT in recurrent breast cancer should be encouraged.     

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients

BackgroundType of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized.Patients and methods1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR).ResultsIndependent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75–0.80). After external validation the accuracy of the nomogram was confirmed.ConclusionThe accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.     

CinéBreast-factors influencing the time to first metastatic recurrence in breast cancer: Analysis of real-life data from the French ESME MBC database

PurposeThe Time to First Metastatic Recurrence (TFMR) could be considered as an indirect reflection of the tumour growth kinetics which plays an important role in cancer. Molecular subtypes such as expression of estrogen receptor are known predictive factors of TFMR. The CinéBreast study aimed to identify predictive factors of the time to TFMR.MethodsThe French Epidemiological Strategy and Medical Economics (ESME) Metastatic Breast Cancer (MBC) Database (NCT03275311) was used, which contains data from a cohort of metastatic breast cancer patients from 2008 to 2016 using retrospective data collection. It is a national multi-centre database. The impact of TFMR on overall survival (OS) since first metastasis was also evaluated.ResultsAmong 16 702 patients recorded in the ESME MBC database, 10 595 had an initially localised breast cancer with hormone receptor (HR) and HER2 status available, with a metastatic recurrence. Median follow up was 56 months. Median TFMR was 59 months (<24: 20%, 24–60: 31%, 60–120: 25%, >120: 24%). HER2+ and TNBC were respectively 4 times and 12 times (p < 0.0001) more likely to have a recurrence within 2 years when compared to the luminal subgroup. Short TFMR and HR-/HER2-subtype significantly correlated with a poor OS in multivariate analysis.Some patients with MBC (20% in HER2+, 10% in ER+/HER2-and <5% in the ER-/HER2-) were long-term survivors in all 3 subgroups.ConclusionsIn this large-scale real-life data study, patients with a TNBC metastatic recurrence had a shorter TFMR. Short TFMR significantly correlated with worse overall survival.     

Additional value of the 70-gene signature and levels of ER and PR for the prediction of outcome in tamoxifen-treated ER-positive breast cancer

BackgroundBreast cancer patients with node positive disease can have an excellent outcome with tamoxifen only. It is unclear whether analysing both the 70-gene signature and hormone receptors provides superior prediction of outcome in tamoxifen-treated patients than either alone.MethodsThree series were evaluated: 121 patients (81% node positive) received adjuvant tamoxifen, 151 patients did not receive tamoxifen (10% node positive) and 92 patients received tamoxifen for metastatic disease.The 70-gene signature was analysed using MammaPrint?. Oestrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry was evaluated following St. Gallen Consensus (Highly Endocrine Responsive: ER and PR ≥ 50%, Incompletely Endocrine Responsive: ER and/or PR low or either one absent).ResultsIn patients treated with adjuvant tamoxifen, both the 70-gene signature (adjusted for Endocrine Response Categories HR 2.17, 95%CI 1.01–4.66) as well as the Endocrine Response Categories (adjusted for 70-gene signature HR 6.35, 95%CI 1.90–21.3) were associated with breast-cancer-specific-survival (BCSS). Also in patients treated with tamoxifen for metastatic disease, combined analysis of the 70-gene signature and ER/PR revealed additional value (multivariate Cox regression, p = 0.013). In patients who did not receive tamoxifen, only the 70-gene signature was associated with outcome.ConclusionIn the series analysed, the 70-gene signature was mainly a prognostic factor, while ER and PR levels were mainly associated with outcome after tamoxifen. Combination of these three factors may improve outcome prediction in tamoxifen-treated patients.     

Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer

IntroductionTraditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC).AimsTo compare NPI and RS for estimating prognosis in ER + breast cancer.MethodsConsecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses.Results1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41–3.4 (486/1471), 30.0% had NPI 3.41–4.4 (441/1471), 10.9% had NPI 4.41–5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140–1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001–1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296).ConclusionIn our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.     

HER2 positivity is not associated with adverse prognosis in high-risk estrogen receptor-positive early breast cancer patients treated with chemotherapy and trastuzumab

Co-expression of human epidermal growth factor receptor-2 (HER2) and hormone receptor (HR) predicted worse prognosis in early breast cancer before trastuzumab was developed. We aimed to investigate whether HER2 positivity was still associated with worse outcome in high-risk estrogen receptor (ER) positive patients treated with trastuzumab and chemotherapy. In the present study, 227 ER+/HER2+ patients treated with trastuzumab and chemotherapy (HER2-pos-T group) and 1097 ER+/HER2-patients treated with chemotherapy alone (HER2-neg group) during 2009 and 2015 were retrospectively enrolled for the comparison of disease-free survival (DFS) and overall survival (OS). At a median follow-up of 59 months, 174 DFS events and 69 deaths were observed. The estimated 5-year DFS rate was 94.2% in the HER2-pos-T group and 87.4% in the HER2-neg group (Log-rank P = 0.014). HER2-pos-T group was associated with significantly better DFS in multivariate analysis (HR 0.38, 95% CI: 0.22–0.67, Log-rank P = 0.001). The estimated 5-year OS rates for the two groups were 97.2% and 95.7%, respectively (Log-rank P = 0.183). In multivariable analysis, patients in the HER2-pos-T group had significantly better OS compared with those in the HER2-neg group (HR 0.40, 95% CI: 0.17–0.95, Log-rank P = 0.037). We concluded that high-risk ER+/HER2+ breast cancer patients treated with chemotherapy and trastuzumab had superior prognosis compared with ER+/HER2-patients. Therefore, HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab.     

Adjuvant endocrine therapy in patients with estrogen receptor-low positive breast cancer: A prospective cohort study

BackgroundLittle is known about the benefits of adjuvant endocrine therapy (ET) in low ER-positive breast cancer (1%–10%) patients. We analyzed the association between ET and breast cancer-specific survival (BCSS) in these patients with respect to the regimen and the duration of ET.MethodsPatients were classified into three groups based on the regimen and duration of ET. The regimens included aromatase inhibitor (AI) monotherapy or sequential tamoxifen followed by an AI (AI/T + AI), or only tamoxifen and no ET. The duration of ET included 2–3 years and >3 years. Multivariate Cox regression analysis was employed to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOf the 10,696 patients diagnosed with breast cancer between 2010 and 2020, 407 women were identified with ER-low positive disease and met the inclusion criteria. During a median follow-up of 5.2 years, patients who received ET improved BCSS. Of them, those with AI/T + AI had increased BCSS compared to patients without ET, after adjusting for demographics and tumor characteristics, especially in ER-low/HER-2-positive breast cancer. After additional adjustment for treatment mode, the association maintained a similar trend. Patients who received >3 years of ET was associated with a better DFS. There was no significant difference in BCSS between patients with 2–3 years and >3 years of ET.ConclusionFor ER-low patients, findings suggest that ET with AI/T + AI may be a reasonable treatment alternative. This effect should be assessed in randomized studies.     

A multifactorial analysis of steroid hormone receptors in stages I and II breast cancer.

It has been shown that the level of estrogen receptors (ER), and to some extent progesterone receptors (PR), correlate to a high degree to the response to endocrine therapy in advanced breast cancer patients. To evaluate the prognostic value of ER/PR in early breast cancer, 80 patients with stages I and II were studied. They all underwent modified radical mastectomy. Patients with stage I disease (negative LN) received no further treatment, while those with stage II received standard adjuvant chemotherapy. All the patients were followed for 4 years. The ER and PR were measured in each primary tumor by the glycerol density gradient method. Values of 10 fmole/mgm protein or greater were considered positive (+) and less than 10 fmole/mgm were considered negative (-). The results revealed: (1) Fifty-two patients (65%) had ER+, of which 44 (85%) were also PR+; 28 patients had ER-, of which 24 were also PR- (p less than 0.0001). (2) ER/PR correlated with age as 71% of the patients over age 50 had ER+/PR+, compared to 33% of those under age 50 (p less than 0.05). (3) Postmenopausal patients had a higher incidence of ER+/PR+. (4) Primary tumors less than 2 cm in size had higher ER+; 71% in those with stage I and 80% in stage II. (5) Fifty-eight per cent (38) of patients with ductal carcinoma had ER+/PR+, compared to 67% (4) with lobular carcinoma. (6) The disease-free survival of patients with ER+ tumors was significantly longer than those with ER- tumors (p less than 0.005) both in positive and negative LN patients. The same was true for PR+ compared to PR- (p less than 0.005), but only in those with stage II disease. The overall survival rates were similarly significant in favor of ER+ and PR+ patients (p less than 0.025), but only in stage II disease. It seems that the status of steroid hormone receptors has a major prognostic factor second only to the LN status.     

Prognosis of Japanese Breast Cancer Based on Hormone Receptor and HER2 Expression Determined by Immunohistochemical Staining

BACKGROUND: We classified Japanese breast cancer patients based on estrogen receptor (ER), progesterone receptor (PR), and HER2 protein expression and compared their prognoses. METHODS: We compared the background and prognostic factors of 600 patients with breast cancer who were assigned to the following groups: luminal A (ER + and/or PR + and HER2-; n = 431; 71.8%), luminal B (ER + and/or PR + and HER2 + ; n = 27; 4.5%), HER2 (ER-, PR-, and HER2 + ; n = 39; 6.5%) and basal-like (BBC; ER-, PR-, and HER2-; n = 103; 17.2%). RESULTS: Background factors did not significantly differ among the groups. Disease-free survival rates were significantly lower for the luminal B, HER2, and BBC subtypes than for the luminal A subtype. Cancer tended to recur earlier and overall survival was significantly lower for the BBC than for the luminal A and HER2 subtypes. Overall survival rates for the luminal B, HER2, and luminal A subtypes were comparable. CONCLUSIONS: The subtype distribution for Japanese and Caucasian patients was comparable. The prognosis for the BBC subtype was poorest among all subtypes. Breast cancer tended to recur earlier for the luminal B and HER2 subtypes than for the luminal A subtype; however, overall survival did not significantly differ among them.     

Adjuvant chemotherapy could benefit early-stage ER/PR positive mucinous breast cancer: A SEER-based analysis

PurposeThe aim of this study was to explore the value of adjuvant chemotherapy in patients with early-stage ER/PR-positive mucinous carcinoma.MethodsWe identified early-stage ER/PR-positive mucinous carcinoma patients in the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity-score matching (PSM) analysis to eliminate selection bias and differences in baseline characteristics. Univariate and multivariate analyses were performed to identify significant prognostic factors. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS), which were evaluated with the Kaplan-Meier method.ResultsAfter propensity score matching, 805 pairs were selected. Patients with early-stage ER/PR-positive mucinous adenocarcinoma in the chemotherapy group had a better OS, but not BCSS, than those in the nonchemotherapy group after PSM (OS: p < 0.001; BCSS: p = 0.285). After stratifying by tumor size and lymph node status, adjuvant chemotherapy could significantly improve the OS of early-stage ER/PR-positive patients with tumors larger than 3 cm (p = 0.004) if they had negative lymph nodes (LNs). For patients positive LNs, the OS was significantly different between the chemotherapy group and the non-chemotherapy group when the tumors were larger than 1 cm (T = 1–2.9 cm, p = 0.006; T＞3 cm, p = 0.049, respectively).ConclusionAdjuvant chemotherapy maybe improves prognosis in patients with negative LNs and tumors larger than 3 cm, or patients with LNs metastasis and tumors larger than 1 cm. We suggest considering clinical characteristics meanwhile when deciding chemotherapy or not. Randomized controlled trials (RCT) are expected to confirm our results in the future.     

Isolated pachymeningeal metastasis from breast cancer: Clinical features and prognostic factors

PurposeTo evaluate the clinical features and prognoses of patients with isolated pachymeningeal metastasis (IPM) from breast cancer.MethodsWe reviewed the medical records of all patients with metastatic breast cancer (MBC) treated from January 2009 to August 2016. Eligibility criteria included diagnosis of pachymeningeal metastasis based on brain magnetic resonance imaging and histologic diagnosis of primary breast cancer. We excluded patients with concomitant parenchymal or leptomeningeal metastases.ResultsThirty-eight patients who matched our inclusion criteria were included in this study. The incidence of IPM in breast cancer was 1.5% of all patients with MBC. The molecular subtype distribution was: triple negative, 29.0%; ER+/HER2−, 44.7%; ER+/HER2+, 18.4%; and ER−/HER2+, 7.9%. All isolated pachymeningeal involvement resulted from the direct extension of skull metastases. The median time to IPM from systemic metastasis was 28.6 (95% CI: 23.6–33.6) months. The median time to IPM from skull metastasis was 5.2 (95% CI: 0–10.9) months. The median overall survival (OS) from IPM was 4.0 (95% CI: 2.5–5.5) months. In patients who received chemotherapy the OS was longer than for those who received radiotherapy or supportive care only [median OS 8.9 (95% CI: 0.0–18.4), 2.8 (95% CI: 0.5–5.0), and 0.8 (95% CI: 0.6–1.1) months, respectively (p = 0.006)]. Multivariate analysis revealed that good performance status and chemotherapy were associated with better survival outcomes.ConclusionStratified evaluation is required for patients with skull metastasis from breast cancer, as pachymeningeal involvement can develop and be associated with unsuspected outcomes.     

Nodal Pathologic Complete Response Rates in Luminal Breast Cancer Vary by Genomic Risk

Background

Although an advantage of neoadjuvant chemotherapy (NAC) is eradication of axillary disease, nodal pCR rates are much lower for ER+/HER2? breast cancer than other subtypes. We sought to evaluate the association of genomic risk with nodal pCR in ER+/HER2? disease.

Methods

Patients with ER+/HER2? clinically-node-positive (cT0-cT4d/cN1-cN3/cM0) breast cancer treated with NAC and surgery 2010–2018 in the National Cancer Database were identified. Low genomic risk was classified as Oncotype Dx Recurrence Score (RS) 0–25, or Mammaprint 70-gene or RS coded as “Low.” High genomic risk included RS >25, or 70-gene or RS coded as “High.” Nodal pCR was compared between patients with high versus low genomic risk by using chi-square tests and multivariable logistic regression.

Results

Of 15,698 patients, genomic risk was available for 692 of 15,698 (4.4%). High genomic risk was similar between patients aged <50 years versus 50+ (50.8% vs. 57.3%, p = 0.10). Nodal pCR was higher in high genomic risk (25.0%) than low genomic risk (10.4%, p < 0.001). This difference was observed both for patients aged <50 years (29.9% vs. 9.8%) and aged ≥50 years (22.7% vs. 10.8%). On multivariable analysis adjusted for potential confounding variables, including age, grade, and PR status, genomic risk was independently associated with decreased odds of residual nodal disease (odds ratio 0.49, p = 0.002).

Conclusions

For patients with node-positive ER+/HER2? breast cancer treated with NAC, nodal pCR was highest in patients aged <50 years with high genomic risk tumors. In contrast, nodal pCR rates were low in patients with low genomic risk tumors, regardless of age. This information may help when counseling patients regarding axillary management.

     

Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab

PurposeThe aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab.MethodsMedical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively.ResultsMedian follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER− and PR−) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33–8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33–8.71) were significant risk factors for development of brain metastasis as the first site of recurrence.ConclusionsIn patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER− and PR−) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.     

Safety of cyclin-dependent kinase4/6 inhibitor combined with palliative radiotherapy in patients with metastatic breast cancer

IntroductionCyclin-dependent kinase (CDK)4/6 inhibitor is a first-line therapy for metastatic ER+/HER2-breast cancer. However, there are limited data on safety of combined radiotherapy (RT) and CDK4/6 inhibition.MethodsWe conducted a retrospective study of women with metastatic breast cancer who received palliative RT within 14 days of CDK4/6 inhibitor use. The primary endpoint was toxicity per Common Terminology Criteria for Adverse Events v5. Secondary endpoints were pain response and local control based on clinical assessment and imaging.ResultsThirty patients underwent 36 RT courses with palbociclib (n = 34 courses, 94.4%) or abemaciclib (n = 2, 5.6%). RT was delivered before, concurrently or after CDK4/6 inhibitors in 7 (19.4%), 8 (22.2%), and 21 (58.3%) of cases with median 3.5 days from RT to closest CDK4/6 inhibitor administration. Median RT dose was 30Gy (range 8–40.05Gy). Treated sites included brain (n = 5, 11.6%), spine (n = 19, 44.2%), pelvis (n = 9, 20.9%), other bony sites (n = 6, 14.0%) and others (n = 4, 9.3%). No acute grade ≥3 non-hematologic toxicity occurred. No increased hematologic toxicity was attributable to RT with grade 3 hematologic toxicities rates 16.7%, 0%, and 6.7% before, during, and 2 weeks after RT completion. All but one patient (29/30) achieved symptom relief. Local control rates were 94.4%, 91.7% at 6 and 12 months.ConclusionsThe use of RT within 2 weeks of CDK4/6 inhibitors had low acceptable toxicity and high efficacy, suggesting that it is safe for palliation of metastatic breast cancer.     

European inter-institutional impact study of MammaPrint

AimTo measure the impact of MammaPrint on adjuvant treatment decisions and to analyze the agreement in treatment decisions between hospitals from 4 European countries for the same patient cohort.MethodsBreast cancer patients were prospectively enrolled and MammaPrint was assessed. Patients' clinical data without and then with MammaPrint results were sent to the different multidisciplinary teams and treatment advice was provided for each patient.ResultsUsing MammaPrint, chemotherapy treatment advice for ER+/HER2- breast cancer patients was changed in 37% of patients by the Dutch, 24% by the Belgian, 28% by the Italian and 35% by the Spanish teams. MammaPrint increased the inter-institutional agreement in treatment advice (chemotherapy or no chemotherapy) from 51% to 75%.ConclusionThe results of this study indicate that MammaPrint impacts adjuvant chemotherapy recommendation. MammaPrint can decrease inter-institutional and inter-country variability in adjuvant treatment advice for breast cancer patients.     

Is breast conservation superior to mastectomy in early stage triple negative breast cancer?

PurposeCompare overall survival (OS) and breast cancer-specific survival (BCSS) outcomes of breast conservative therapy (BCT) and mastectomy in a large cohort of patients with early-stage triple negative breast cancer (TNBC), using a propensity score-based matching approach.MethodsSurveillance, Epidemiology, and End Results (SEER) database was used to study the role of RT in early stage TNBC. Primary end points were OS and BCSS. Cox proportional hazard regression models and Kaplan-Meier plots were used to generate the desired outcomes. Propensity score matching was done to minimize bias.Results12,761 patients with T1-2N0M0 TNBC as their first malignancy were retrieved. Of these 7237 had lumpectomy with RT, and 5524 had mastectomy only. Age, race, marital status, tumor laterality, grade and stage, and receipt of chemotherapy were prognostic variables for OS and BCSS. Among 4848 matched subjects, the 5-year OS was significantly higher in patients with lumpectomy and RT (89%) compared to mastectomy alone (84.5%) (p-value <0.001). Similarly, BCSS was significantly higher in patients with lumpectomy and RT (93%) compared to mastectomy alone (91%) (p-value <0.001). On subgroup analysis, patients who are younger than 40 had similar survival outcomes after either mastectomy alone or lumpectomy with RT. However, those who are older than 60, have any grade or T stage had better survival outcomes with lumpectomy and RT.ConclusionsOverall, lumpectomy followed by RT is associated with better OS and BCSS compared to mastectomy in T1-2N0M0 TNBC patients. Further research is needed to determine the optimal treatment strategy for specific patient subgroups.     

Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients

PurposeTo assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival.MethodsPreoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355).ResultsCPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate = .11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P = .143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P = .017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P = .020) for OS and 1.10 (95% CI = 1.02, 1.18; P = .012) for IDFS.ConclusionCPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.