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Background: Breast cancer is the second most common cause of central nervous system (CNS) metastasis, leading to a significant decrease in survival rate. High risk groups for CNS involvement include younger age, human epidermal growth factor 2 (HER2) over-expression, estrogen receptor (ER) and progesterone receptor (PR) negativity, high histologic grade, and presence of systemic metastases. Young age at diagnosis of breast cancer is associated with more aggressive biological behavior and worse prognosis than in the elderly. However, data are limited regarding CNS involvement in this group of patients. Although it could be expected that younger patients would also have a poor prognosis after the diagnosis of CNS metastases, earlier studies have demonstrated conflicting results, some with favorable outcomes for this unique group. In this study we aimed to explore the differences in the patterns and outcome of CNS involvement according to age at diagnosis of breast cancer (≤45 years vs. >45 years). Methods: A retrospective database of consecutive breast cancer patients who were treated in our institute and were diagnosed with CNS metastases during 2006-2019 was generated. Data analyzed included age at diagnosis of breast cancer, age at diagnosis of CNS involvement, histopathological factors (histology, grade, hormone receptor and HER2 status), treatments given before and after CNS involvement, characteristics of CNS involvement (location, number of brain deposits, clinical manifestations), overall survival, time to CNS progression, and survival after diagnosis of CNS disease. Results: Study cohort was comprised of 174 patients: 65 patients were age≤45 and 109 patients were older than 45 at breast cancer diagnosis. The percentage of patients with triple-negative breast cancer was higher among the younger age group (24.6% vs. 14.7%). Median overall survival from breast cancer diagnosis was significantly longer for younger patients [117.1 months (95% CI 67.2-167) vs. 88 months (95% CI 65.6-110.4), p=0.017]. Median time from breast cancer diagnosis to development of CNS metastases was also significantly longer in the younger age group [58.1 months (95% CI 46.5-69.6) vs. 37.5 months (95% CI 22.9-52.2), p=0.021]. Median survival as measured from time of CNS involvement was 18.7 months (95% CI 10.8-26.6) in the younger group vs. 11.1 months (95% CI 7.8-14.5) in the older patients (p=0.341). Survival of patients with triple-negative breast cancer from time of CNS metastases diagnosis was significantly longer for the younger age group [22.5 months (95% CI 1.2-43.8) vs. 7.9 months (95% CI .77-15.1), p=0.033]. The number, location and clinical presentation of CNS metastases were not statistically different between the two groups. Systemic and CNS-directed treatment approaches were also similar. Conclusion: While the presentation of CNS metastasis was similar between the different age groups, younger patients had significantly longer CNS-free interval and longer overall survival. Numerically, after diagnosis of CNS involvement younger patients had longer survival, but the difference was statistically significant only for patients with triple-negative disease. Citation Format: Matan Ben-Zion Berliner, Shlomit Yust-Katz, Inbar Lavie, Alexandra Amiel, Dalia Zoref, Daniel Hendler, Hadar Goldvaser, Michal Sarfaty, Ofer Rotem, Olga Ulitsky, Tali Siegal, Victoria Neiman, Rinat Yerushalmi. Central nervous system metastases in breast cancer: The impact of age on patterns of development and outcome [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-41.

Background Combination of pertuzumab, trastuzumab and chemotherapy is standard of care for first-line treatment of patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Most randomized studies used combination of taxanes and anti HER2 targeted treatment as 1st line treatment. The combination of vinorelbine, trastuzumab and pertuzumab has shown anti-tumor activity in a phase 2 trial. No trials have compared outcomes between vinorelbine to taxane in combination with pertuzumab and trastuzumab. Methods We retrospectively evaluated all patients with metastatic HER-2 positive breast cancer treated in two institutions between 3/2013 and 3/2018. Patients' clinical data were obtained from electronic medical records. We identified patients who were treated with vinorelbine (oral or intravenous) or a-taxane (docetaxel or paclitaxel) in combination with trastuzumab and pertuzumab as a first-line treatment. We compared progression free survival (PFS), overall survival (OS) and toxicity profiles between the two groups. Results The study included 120 patients (73 in the taxane and 47 in the vinorelbine group). There were several between-group differences: 65% of the taxane group patients were metastatic at diagnosis compared to 40% in the vinorelbine group (p=0.008), 18% of the taxane group received trastuzumab in the adjuvant setting vs. 45% in the vinorelbine group (p=0.003). More patients in the taxane group were asymptomatic (43.4% vs 23.4%, p=0.04). PFS was significantly longer in the taxane group compared to the vinorelbine group (35.4 months vs 13.9 months, p=0.0005). OS was also longer in the taxane group, but difference did not reach statistical significance (48.8 months vs 34.5 months, p=0.13). In the subgroup of patients with recurrent disease (excluding patients with de-novo metastatic disease), there was no difference for OS (32.6 vs 33.1 months for taxane and vinorelbine, respectively). Toxicity profiles differed between the groups, with more patients in the taxane group experiencing diarrhea, peripheral neuropathy and asthenia, and more patients in the vinorelbine group experiencing neutropenia. Discontinuation of chemotherapy due to toxicity was more common in the taxane group compared to the vinorelbime group. (38% vs. 17%, p=0.015). Conclusions In this retrospective analysis, first-line treatment with taxane combined with trastuzumab and pertuzumab for HER-2 positive metastatic breast cancer resulted in improved outcomes compared with the combination of vinorelbine, trastuzumab and pertuzumab. The vinorelbine arm revealed a favorable toxicity profile. Patients with recurrent disease (excluding de-novo metastatic disease) had similar outcomes with either chemotherapy. A randomized study is warranted. Citation Format: Daniel Jack Reinhorn, Irina Kuchuk, Judit Prus, Michal Sarfaty, Hadar Goldvaser, Ofer Rotem, Daniel Hendler, Dalia Zoref, Victoria Neiman, Tzipora Shohat, Olga Ulitsky, Shlomit Yust-Katz, Bella Nisenbaum, Maya Gottfried, Rinat Yerushalmi. Taxane versus vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with metastatic HER2-positive breast cancer - A retrospective two-center study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-33.