Abstract Background: Invasive lobular carcinoma (ILC) represents the second most common BC subtype and is often characterized as hormone receptor positive and HER2−negative. However a small subset of ILC is found to be HER2+. Isolated case reports have demonstrated high responsiveness to trastuzumab in patients with advanced HER2+ ILC. The HERA trial compares 1 or 2 years of trastuzumab treatment with observation and 1 versus 2 years of trastuzumab treatment after standard chemotherapy in women with HER2+ breast cancer. We sought to evaluate the incidence of HER2+ ILC and the magnitude of trastuzumab benefit in HER2+ ILC in the context of the HERA trial. In addition, we sought to describe the pattern of hormone receptor positivity in the subsets of ILC and invasive ductal carcinoma (IDC) Methods: The database used in the analysis had a clinical cut-off date of 9th June 2008 and 4-year median follow-up (Gianni et al., 2011). Patients randomized to the 1-year trastuzumab and observation arms were included in the present analysis. Central assessment of hormone receptor status was considered. Histological BC subtype was assessed locally. Results: Of the 1703 women randomized to one-year of trastuzumab and 1698 to observation, 5.5% (n=187) and 94.5% (n=3213) were diagnosed as HER2+ ILC and IDC, respectively. Central hormone receptor status was available in 88.3% (n = 2838) of IDC and 86.1% (n=161) of ILC. ER and/or PR positivity was more common in ILC than IDC (63.4% [102/161] vs. 46.3% [1314/2838]; p<0.001). Allred scores for ER are shown in the table below. The DFS hazard ratios comparing one year of trastuzumab versus observation were 0.63 (95% CI 0.34−1.14) for ILC and 0.77 (95% CI 0.67−0.89) for IDC. There was no evidence of an interaction between histological subtype and trastuzumab benefit (interaction [subtype lobular and subtype ductal and not lobular] p=0.49). Conclusion: HER2+ ILC accounts for 5.5% of patients included in a large population of over 3,000 HER2+ BC. While only a limited number of patients with ILC was enrolled, this analysis suggests an increased ER positivity in ILC compared to IDC. There was no suggestion that patients with HER2+ ILC derived a different magnitude of benefit from adjuvant trastuzumab when compared to the HER2+ IDC cohort. The lack of central pathology review for BC subtype assessment is a caveat of our study. Future research in the field of ILC and particularly in the HER2+ subset should be encouraged. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-01.

Abstract Background: 1-year of adjuvant trastuzumab (T) is the standard of care in managing patients (pts) with early HER2−positive breast cancer (BC). As T is not known to alter fertility, pts with childbearing potential could become pregnant during or following treatment with T. Cases of oligohydramnios, some associated with fatal pulmonary hypoplasia of the fetus have been reported in women receiving T during pregnancy (preg). Here we report the outcome of preg in all pts enrolled in the HERA trial. Methods: Pregnancies in the HERA trial are reported on a distinct “pregnancy form” for up to 10 years following T completion. The form includes information on approximate date of conception, preg course & outcome, fetal measurements at birth, and congenital anomalies. Any missing data were retrieved from the study site, if available. For this analysis, pts were grouped into 3 groups: 1) preg during and up to 3 months after T, 2) preg > 3 months of last T dose, and 3) preg with no prior exposure to T. Results: By March 2010, 70 preg were reported in 58 out of 5102 pts randomized. Five, 30 and 7 completed preg were reported in groups 1, 2 & 3 respectively. As per protocol, all pts on T were required to use adequate contraceptive measures, yet 16 pts became pregnant during the course of T and up to 3 months thereafter. The percentage of completed preg was lowest in group 1, with 4 spontaneous and 7 induced abortions. In group 2, preg occurred at a mean of 29 months following completion of T, with 6 spontaneous and 4 induced abortions. In group 3, abortion was induced in 3 pts and no spontaneous abortions reported. Across all 3 groups, all but 1 spontaneous abortion occurred during the 1st trimester. Two congenital anomalies were reported; a Down's syndrome in a 43 year old pt >5 years after completing T for which abortion was induced, and one with partial fusion of the 2nd and 3rd toe born to a pt in group 3. Conclusions: Unintentional exposure to T during preg may be associated with spontaneous abortion, yet the numbers remain low to draw firm conclusions (spontaneous abortion rate in general population is up to 20%). No oligohydramnios or anomalies were observed in group 1. While an increased risk of oligohydramnios has been reported when T is administered after the 1st trimester, T administered to Cynomolgus monkeys during organogenesis did not cause fetal harm (Pentsuk et al; 2009). Nevertheless, women of childbearing potential should be advised to use effective contraception during and up to 6 months after treatment with T. On the other hand, prior exposure to T did not appear to affect the preg course or outcome. We are planning to collect information from the other T adjuvant trials to confirm our findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-01.