See Appendix for individual names.Background: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods:In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results:Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nabpaclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%).Conclusions: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.ClinicalTrials.gov: NCT01572038.

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Background: Anthracyclines belong to the most effective therapies for patients (pts) with breast cancer. Toxicity limits its use in elderly women where, beside nausea, vomiting, hair loss and the risk for infections, cardiotoxicity is of special concern. Caelyx is pegylated liposomal doxorubicin, a formulation diminishing the risk for the mentioned side effects but with a risk for skin toxicity known as Palmar-Plantar Erythrodysesthesia (PPE). As Caelyx is generally well-tolerated, we investigated its value as first-line CT in women 65 years or older. We also collected a variety of tumor and patient markers in search of predictors of outcome and toxicity. Methods: Women age ≥65 years, with inoperable locally advanced or metastatic breast cancer with performance status (PS) WHO 0-2, measurable disease according to RECIST or WHO criteria for bone metastasis or non-measurable disease, Left Ventricular Ejection Fraction (LVEF) ≥50% and normal organ function, received 40 mg/m2 Caelyx every 28 days. Pts underwent tumor evaluation including LVEF every 3 months. Primary endpoint was time to treatment failure (TTF) defined as progression of disease or unacceptable toxicity. Secondary endpoints were safety, response rate (RR), time to progression (TTP), overall survival (OS), and analysis of treatment predictive factors in tumor tissue. Also the ABCB1 (=Multi Drug Resistance gene 1) single nucleotide polymorphism (SNP) was investigated. Results: 25 women were included in the study. Median age was 72 years (range 65-81). The median TTF was 5.5 months and the mean number of cycles received was 7.4 (range 1-21). 22 pts were followed by RECIST or a combination of RECIST and WHO. Of these one achieved a partial response (PR) and 11 stable disease (SD). The median TTP was 5.7 months and the median OS was 20.6 months. The majority of adverse events (AE's) were mild to moderate and transient, the main toxicities being nausea 60% (grade I/II/III 24/32/4), fatigue 56% (40/12/4) and PPE 52% (24/20/8). Clinically significant changes in LVEF were noted in three pts. Severe AE's occurred in 8 pts. And the dose was reduced due to toxicity in 4 pts. Analysis of the ABCB1 SNPs revealed that pts with homozygous mutation for SNP G2677T had significantly shorter time to treatment failure and time to progression as compared to the rest of the pts. Those with the 3435T/T genotype were more susceptible to moderate to severe PPE (5 out of 8 with SNP 3435T/T as compared to 2 out of 16 non-3435T/T pts). Conclusion: Breast cancer in elderly patients in need of CT can be challenging because of the risk of toxicity, reduced quality of life and also the lack of tumor response. To be able to select the right patient for a certain therapy would be essential. We treated 25 elderly women with advanced breast cancer with Caelyx with acceptable toxicity and efficacy. We also found that SNPs in ABCB1 correlated with both TTP and the risk of PPE, thereby indicating that the ABCB1 genotype could be a predictive factor for treatment with Caelyx in elderly women. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-07.

Background: The benefit of radiotherapy in older women with endocrine responsive early breast cancer treated with breast-conserving surgery and endocrine therapy is unclear. The aim of this study was to verify if omission of radiotherapy in a predefined cohort of patients with good prognosis early breast cancer after breast conservation is safe. Methods: Eligibility criteria were: consecutive patients with age ≥ 65 years, breast-conserving surgery (sector resection + sentinel node biopsy), clear margins, unifocal T 1 N0, Elston grade 1 and 2, estrogen receptor-positive. After informed consent adjuvant endocrine therapy, either tamoxifen or an aromatase inhibitor, was prescribed for 5 years. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer, recurrence-free survival (RFS) and overall survival (OS). Results: Between 2006 and 2012, we included 603 women from 14 Swedish centers. Two patients did not fulfill the inclusion criteria and were excluded from the analysis. Median age was 71 years (range 65 to 90). At a median follow-up of 59 months (range 2 to 110) 13 IBTR (cumulative incidence at five years, 1.3% (95% CI, 0.6% to 2.7%), 4 regional recurrences (one combined with IBTR), 2 distant recurrences both without IBTR or regional recurrence and 11 contralateral breast cancers was observed. Twenty-nine patients were diagnosed with tumors of other origin. Seven of them were endometrial cancers. There were 39 deaths. Only one of the deaths (2.6%) was due to breast cancer and 11 (28.2%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.9% (95% CI, 91.4% to 95.7%). Conclusion: This study demonstrates, with a median follow-up of 59 months, that breast-conserving surgery and endocrine therapy without radiotherapy is a safe treatment option in women with early breast cancer and favorable histopathology aged ≥ 65 years. The risk of IBTR is comparable to the risk of contralateral breast cancer. The low rate of breast cancer deaths indicates that breast cancer mortality is of secondary importance in this subset of women. Citation Format: Villman KKA, Wickberg Å, Killander F, Lindman H, Bjöhle J, Edlund P, Tennvall-Nittby L, Bachmeier K, Carlberg M, Blomqvist C, Ahlgren J, Liljegren G. Omitting radiotherapy in women ≥ 65 years with early breast cancer and favorable histopathology after breast-conserving surgery, sentinel node biopsy and adjuvant endocrine therapy is safe [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-05.