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Purpose: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. Methods: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). Results: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p < 0.0001), HER2 negativity (HR = 0.582, p = 0.024), absence of LN (HR = 0.751, p = 0.008) and liver involvement (HR = 0.746, p = 0.013), older age at capecitabine start (HR = 0.925, p < 0.0001) and younger age at diagnosis of MBC (HR = 0.935, p = 0.001) were significant features of longer TTP. Conclusion: Our data display relevant clinical-pathological features associated with DR and TTP in patients receiving capecitabine monotherapy for MBC. [ABSTRACT FROM AUTHOR]

Poster: Physics track: Intra-fraction motion management PO-1590: Spirometer guided breathhold breast VMAT on Halcyon verified with portal images and surface tracking L. Delombaerde, S. Petillion, C. Weltens, T. Depuydt. [Extracted from the article]

Background: Treatment of breast cancer includes many options and shared decision making is becoming standard practice. Within the context of treatment individualization, the omission of radiotherapy (RT) can be considered. It is thereby of great importance to correctly foresee the side effects attributed to RT. Data from longitudinal studies with contemporary techniques however are sparse. The purpose of the present study was to evaluate patient-reported outcome measures (PROMs) and long-term aesthetic outcome (AO) related to RT in the breast-conserving therapy (BCT) setting for breast cancer over time.Methods: Patients treated with BCT between April 2015 and April 2016 were prospectively included in the cohort. Evaluations were made at six time points: at baseline (before RT), during and at the end of RT, between 3 and 6 months, 1 year and 2 years after RT. AO was scored by the patient and by the BCCT.core software. Further PROMs were measured with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30/-BR23 and the Body Image after Breast Cancer Questionnaire BIBCQ. Patients were evaluated over 2 years. First, we assessed the evolution in time. Second, we tested the differences in mean scale scores of the PROMs between patients with a favourable and an unfavourable AO.Results: One hundred seventy-five patients were included in the analysis. At baseline, unsatisfactory levels were already present for several scales. Most unsatisfactory PROMs improved up to 1 year after RT. Complaints of fatigue increased at the start but decreased up to a lower level than that at baseline up to 1 year after RT (mean difference (MD) 7.6, - 12.3, respectively). Cognitive functioning showed a small decrease at the start with no further significant decrease (MD - 4.73, - 0.21, respectively). Breast symptoms significantly increased during RT but decreased afterwards up to 2 years after RT to lower values than those at baseline and were then considered satisfactory (MD 15.6, - 19.7, - 4.1, respectively). AO scored as PROM associated with BCCT.core and with the body image measures.Conclusions: The study suggests that quality of life and body image are temporarily impaired due to RT. Around one third of patients score their long-term AO as unfavourable. These results should be discussed with the patient and could help in the decision making of the treatment plan and in the clarification of the patient's expectations. [ABSTRACT FROM AUTHOR]

Background Many easily measurable and readily available factors are now established as being prognostic in primary operable breast cancer. We here applied the 2011 St Gallen surrogate definition for breast cancer subclassification using tumor grade instead of Ki67. Patients and methods Four thousand three hundred and eighteen consecutive patients who had surgery for primary operable breast cancer (1 January 2000 and 31 December 2009) in UZ Leuven excluding primary metastastic male breast cancers and those receiving neoadjuvant therapy. Five different surrogate phenotypes were created using the combined expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 together with tumor grade. Disease-free interval (DFI), distant metastastis-free interval (DMFI), locoregional relapse-free interval (LRRFI), breast cancer-specific survival (BCSS) and overall survival (OS) were calculated. Results Surrogate phenotypes present with significant differences in DFI, DMFI, LRRFI, BCSS and OS. ‘Luminal A’ tumors presented with the best outcome parameters but the effect weakened at longer follow-up. Conclusions The four surrogate markers, agreed upon by the 2011 St Gallen consensus, defined five prognostic surrogate phenotypes in a large series of consecutively treated breast cancer patients. Their prognostic value changed with longer follow-up. The added value of gene expression profile over classical pathological assessment remains to be defined. [ABSTRACT FROM AUTHOR]

Background: We studied the stellate ganglion block (SGB) recently suggested for the treatment of severe vasomotor symptoms and sleep disturbances in breast cancer survivors. Following an initial pilot study, which focused on the acceptability and safety of SGB for this important problem, we evaluated its short- and long-term efficacy. Materials and methods: Postmenopausal breast cancer survivors with severe vasomotor symptoms resistant to standard nonhormonal pharmacological intervention were eligible. Diaries were used to measure daily hot flash scores (frequency and intensity) and sleep quality (Pittsburgh Sleep Quality Index) during scheduled visits at baseline, 1, 4, 12 and 24 weeks following the SGB. Efficacy data were analyzed using longitudinal regression models. Results: Thirty-four patients participated and none refused the SGB procedure. Most patients received more than one SGB. The pilot study found SGB to be safe. In the main study, hot flash scores were reduced from baseline by 64% [95% confidence interval (CI) −74% to −49%] and 47% (95% CI −62% to −27%) at weeks 1 and 24, respectively. The odds ratio of better sleep quality relative to baseline was 3.4 at week 1 (95% CI 1.6–7.2) and 4.3 at week 24 (95% CI 1.9–9.8). Conclusion: In the short term, SGB appears to be an effective treatment with acceptable morbidity for some breast cancer survivors with therapy-resistant vasomotor symptoms and/or sleep disturbances. Although sleep quality was maintained out to 24 weeks the efficacy of SGB for hot flashes was reduced over time. A randomized controlled trial is needed to confirm these findings. [ABSTRACT FROM PUBLISHER]

Background: To evaluate capecitabine–docetaxel (XT), with trastuzumab (H) in human epidermal growth factor receptor 2 (HER2)-positive disease, in inoperable locally advanced breast cancer (LABC).Patients and methods: Patients received up to six neoadjuvant 21-day cycles of capecitabine 900 mg/m2 twice daily, days 1–14, plus docetaxel 36 mg/m2, days 1 and 8. Patients with HER2-positive disease also received trastuzumab 6 mg/kg every 3 weeks. The primary end point was pathologic complete response (pCR) rate, evaluated separately in HER2-negative and HER2-positive cohorts. Secondary end points included clinical response rates and tolerability.Results: The pCR rate was 15% [95% confidence interval (CI) 7–28] in 53 patients receiving XT and 40% (95% CI 26–55) in 50 patients receiving HXT. After neoadjuvant therapy, 50 patients receiving XT and 45 receiving HXT underwent surgery. No unexpected toxicity was observed: the most common grade ≥3 adverse events were diarrhea/mucositis (30% and 20%, respectively) and grade 3 hand–foot syndrome (11% and 6%, respectively). Disease-free survival and overall survival were similar with XT and HXT after median follow-up of 22 months in the XT cohort and 21 months in the HXT cohort.Conclusion: Neoadjuvant XT (HXT in HER2-positive disease) is highly effective in inoperable LABC, demonstrating pCR rates of 15% and 40%, respectively. This non-anthracycline-containing regimen offers obvious benefits in early disease, where avoidance of long-term cardiotoxicity is particularly important. [ABSTRACT FROM AUTHOR]

Background: Decisions about systemic treatment in women with metastatic breast cancer are currently based on the presence of estrogen receptors (ER), progesterone receptors (PR) or Human Epidermal growth factor Receptor 2 (HER2 receptors) in the primary tumor. Recently, several studies have reported significant discordances in ER, PR and HER2 status between the primary tumor and metastatic lesions and this may vary by metastatic site. Prognostic implications remain unclear although alterations in ER, PR and/or HER2 can influence metastatic management. This study represents one of the largest studies evaluating how frequent receptor discordances occur in liver metastasis, whether this alters therapeutic options and impacts prognosis. Patients and methods: 246 breast cancer patients with histological confirmed liver metastasis were analyzed in this retrospective study. Immunohistochemistry (IHC) and/or FISH were used to determine ER, PR and HER2 receptor status. We excluded patients when comparison between receptors of primary tumor and metastasis was impossible due to missing data (n = 85), when liver metastasis did not originate from breast cancer (n = 36) and when pathology was obtained from autopsy specimens (n = 38). Results: 87 patients had matched tissue samples of primary tumor and liver metastasis with possible comparison of at least one of the receptors. Table 1 summarizes changes in ER, PR, HER2 between primary and metastatic lesion. Discordance in receptor status was associated with shorter time to death (63.3 months) compared to the concordant group (75.5 months). Conclusions: A significant proportion of ER and PR show discordance between primary tumor and liver metastasis. However we could not establish the same level of discordance for the HER2 receptors as in other studies. In general, only about 1 in 5 patients gained new (endocrine or targeted) therapeutic options. Tissue confirmation remains important to evaluate whether metastatic disease has become endocrine insensitive (in approximately 1 in 5 patients), avoiding unnecessary delay in chemotherapy. Discordance in receptors may be associated with inferior prognosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: The five prognostic surrogate phenotypes, defined by the 2011 St Gallen consensus, predict metastatic relapse following early breast cancer treatment (Brouckaert et al Ann Oncol 2012). It is unknown to what extent these surrogate phenotypes defined on the primary tumor predict metastatic survival (MS) in a cohort of consecutive women with metachronous metastases. PATIENTS & METHODS: All 4318 patients with primary operable breast cancer, diagnosed between 01-01-2000 and 31-12-2009 and treated in our center were prospectively entered in our institutional database. We included 345 patients with a (distant) metastatic relapse during their follow-up. We observed metastatic survival as the time between the diagnosis of the relapse and death. Tumor subtype was defined according to the 2011 St Gallen recommendations in 5 groups: luminal A (ER+/HER2-, grade 1-2), luminal B1 (ER+/HER2-, grade 3), luminal B2 or luminal-HER2 (ER+/HER2+), HER2-like (ER-/HER2-) and triplenegative. We focused on the value of the primary tumor subtype as a major prognostic determinant, but also assessed age at diagnosis, tumor size, lymph node involvement, tumor subtype, PR-status, primary detection (screening vs. palpation), histology, adjuvant therapy, distant-metastasis free interval (DMFI), first-line metastatic hormonal therapy, recurrence sites (isolate or multiple) and metastasis detection (clinical vs. biochemical). RESULTS: In our cohort, we recorded a median metastatic survival (MS) of 22.3 months (95% CI: 19.7-25.6) and a 5-year survival probability of 15%. Significant differences in median MS were noted when considering the primary tumor subtype (cf. table). We observed an independent prognostic effect for multiple recurrence sites (HR = 1.78, 95% CI 1.37-2.32), first-line metastatic hormonal therapy (HR = 0.30, 95% CI 0.18-0.49), DMFI (HR = 0.92 CI 0.85-0.98) and, finally, primary tumor subtype. CONCLUSION: Our results showed that primary tumor subtype, DMFI, solitary recurrence and first-line metastatic hormonal therapy act as independent prognostic factors in metastatic breast cancer. In order to overcome the biological complexity of metastatic breast cancer, we must appreciate the primary tumor subtype in our therapeutic approach. [ABSTRACT FROM AUTHOR]

Introduction: Although known to hold prognostic value, PR status is not used to discriminate luminal A from luminal B HER2 negative breast cancers. We will here assess whether PR (and also detection mode) is an independent prognostic variable in luminal HER2 negative breast cancer and whether the prognostic value of PR is grade dependent. Patients and methods: Primary operable breast cancer patients diagnosed between 1/1/2000 and 31/12/2009 treated in UZ Leuven were retrieved from the prospectively managed database (n = 4318). Her-2 status was missing in 93 and ER/PR in 2 patients. Of the remaining patients, 3330 were luminal (ER and/or PR positive) HER2 negative (full cohort details: Brouckaert O., et al. Ann Oncol. 2012 Apr 6). Missing values were observed in 137 patients (4.1%), and these were imputed using 'multivariate imputation by chained equations'. A competing risks proportional hazards model was used for multivariable analysis (includes age, size, grade, screening, palpability, nodal status, histology, type of surgery, radiotherapy, endocrine and chemotherapy) of distant metastasis free interval (DMFI) and breast cancer specific survival (BCSS). We used a predefined set of predictors, investigated non-linearity of the predictor effects, checked the proportional hazards assumption, and tested for interactions with grade. Results: Median follow-up was 76 months and 5-year survival probability 93%. PR is an independent prognostic variable but this is grade dependent for DMFI, but not for BCSS (interaction p = 0.15), although PR positivity was mainly protective for grade 3 breast cancers again (table 1). Palpability is a strong prognostic variable for DMFI and BCSS and was strongly correlated with screen detection (yes/no) and here, we found no evidence of grade dependency. Conclusion: PR status and palpability may further refine prognosis of patients with luminal HER2 negative breast cancers. For PR, prognostic value is grade dependent, but for palpability, this is grade independent. [ABSTRACT FROM AUTHOR]

Background: Whether age is an independent prognostic factor in early breast cancer remains controversial. Different cut-off values have been suggested in different studies and few studies assessed its value in triple negative breast cancer and other phenotypes. Methods: We included all primary operable breast cancer patients from our prospectively managed database in UZ Leuven, Belgium. We excluded male patients, patients treated elsewhere first, patients treated with primary systemic treatment first. We assessed the effect of age as a continuous and categorical variable for distant metastasis free interval (DMFI), locoregional free interval (LRRFI) and breast cancer specific survival (BCSS) in multivariable analysis (correcting for phenotype, tumor size, nodal status, chemo-, endocrine-, radiotherapy, type of breast and axillary surgery). We assessed the effect of age for DMFI, LRRFI and BCSS in basal-like breast cancer and other phenotypes. Results: We included 4318 patients with a mean/median age of 58/ 57 years (1170 patients were younger than 50 years) and with a median follow-up of 6,0 years. Multivariate analysis confirmed age as an independent prognostic variable for LLRFI (HR1.91; 95% CL:1.33-2.74; p = 0.0005), DMFI (HR:1.77; 95% CL:1.33-2.36; P < 0.0001) and BCSS (HR:2.35; 95% CL:1.66-2.74; P < 0.0001). The optimal cut-off value is 41 years for LLRFI and BCSS and 44 years for DMFI. We did not find an independent prognostic value for age in triple negative breast cancer regarding DMFI and LRRFI. Results for other subtypes are subject to currently ongoing analyses. Conclusions: Overall, young age in primary operable breast cancer patients is an independent prognostic value for DMFI, LRRFI and BCSS after adjusting for known prognostic factors. In triple negative breast cancer, age did not retain independent prognostic value for DMFI and LRRFI. [ABSTRACT FROM AUTHOR]

Background: In primary operable breast cancers, Adjuvant!Online (AOL) uses demographics and clinic-pathological markers to predict the 10-year breast cancer specific survival (BCSS) with and without adjuvant systemic therapy. Grade 2 BC is a difficult group for adjuvant treatment decisions. We compared the observed with the AOL-estimated BCSS rate in our centre in consecutive women primary operated for a grade 2 BC. Patients and Methods: All patients with grade 2 primary operable breast cancer from UZL diagnosed between 1/1/2000 and 31/3/2002. After 10 years of follow-up, patients were evaluated for BCSS and dead from other cause. For each patient, the adjuvant! Online algorithm (version 8) was applied to predict BCSS taking the patients' adjuvant therapy into account. Adjuvant! Online was validated by assessing the calibration and discrimination. Discrimination was assessed by the area under the ROC curve. The expected BCSS rate was obtained by averaging the predicted probabilities of BCSS. Next, logistic calibration was performed by predicting observed BCSS within 10 years of follow-up with the odds of the predicted probability of BCSS (odds BCSS). In this analysis, the intercept should be 0 and the coefficient for odds BCSS 1 for perfect calibration of the predicted probabilities. A likelihood ratio test is used to test the null hypothesis of perfect calibration. Results: Six patients were lost to follow-up. The median age at diagnosis of the remaining 445 patients was 56 years (IQR 48 to 67 years, range 26 to 89 years). In 433/445 cases (97%), the prediction from AOL was available. The median AOL predicted probability for BCSS was 89.1% (IQR 83.2 to 94.6%, range 20.3 to 98.9%). The observed BCSS rate was 93.3% whereas the AOL-expected rate was 86.7%. The likelihood ratio test for perfect calibration was statistically significant (p < 0.0001), with an intercept of -1.55 (95% Cl -2.33 to -0.84) and a coefficient for odds BCSS of 0.55 (95% Cl 0.19 to 0.92). AOL strongly underestimated the probability of BCSS. The AUC was 0.65 (95% Cl 0.53 to 0.76). For patients that did not die from BC within 10 years, the median estimated BCSS probability by AOL was 89.6% (IQR 83.5 to 94.6 %), whereas for patients that died from BC the median estimated probability was 83.9 % (IQR 77.9 to 94.5%). Conclusion: Although Adjuvant! Online achieved moderate discrimination between those that did and those that did not die from BC within 10 years FU, it clearly underestimated the probability of BCSS in our sample. [ABSTRACT FROM AUTHOR]