Relationship of ethnicity and other prognostic factors to breast cancer survival patterns in Hawaii.

The survival experience of 2,956 invasive breast carcinoma cases identified among the 5 major ethnic groups in Hawaii between 1960 and 1979 was studied. The study population consisted of 1,174 Caucasian, 972 Japanese, 458 Hawaiian, 226 Chinese, and 126 Filipino women. A multivariate analysis based on the proportional hazards regression model revealed that after simultaneous adjustment for stage of disease, age, and socioeconomic status (SES), Filipino and Hawaiian patients had significantly poorer survival than Japanese and Caucasian patients. Hawaiian women also had a significantly poorer survival than Chinese women. Survival was higher in patients between the ages of 45 and 54 years compared to those younger or older, in patients with localized tumors compared to those with more advanced tumors, and in patients with middle or high SES compared to those with the low SES. Histology and marital status were not associated with survival. The possibility that other factors such as obesity, estrogen receptor status, treatment, and nutritional and hormonal status could explain the remaining observed racial differences in breast cancer survival is discussed.

Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome.

Aberrant expression of cyclin D1 protein is a common feature of breast cancer. However, the CCND1 gene encodes two gene products, cyclin D1a and cyclin D1b, which have discrete mechanisms of regulation and impact on cell behavior. A polymorphism at nucleotide 870 in the CCND1 gene, rs603965, influences the relative production of the encoded proteins and can impart increased risk for tumor development. Here, the impact of both the G/A870 polymorphism and cyclin D1b protein production on breast cancer risk, disease phenotype and patient outcome was analysed. In a large multiethnic case-control study, the G/A870 polymorphism conferred no significant risk for breast cancer overall or by stage or estrogen receptor (ER) status. However, the cyclin D1b protein was found to be upregulated in breast cancer, independent of cyclin D1a levels, and exhibited heterogeneous levels in breast cancer specimens. High cyclin D1a expression inversely correlated with the Ki67 proliferation marker and was not associated with clinical outcome. In contrast, elevated cyclin D1b expression was independently associated with adverse outcomes, including recurrence, distant metastasis and decreased survival. Interestingly, cyclin D1b was particularly associated with poor outcome in the context of ER-negative breast cancer. Thus, specific cyclin D1 isoforms are associated with discrete forms of breast cancer and high cyclin D1b protein levels hold prognostic potential.

Breast cancer survival among Hawaii Japanese and Caucasian women. Ten-year rates and survival by place of birth.

Unlike past breast cancer survival comparisons between Japan and the United States, a recent study in Hawaii showed that Japanese women did not retain their survival advantage over Caucasian women after adjustment was made for stage at diagnosis. To test whether this finding in Hawaii was due to the limited duration of the follow-up (five years) or to the effects of migration, the survival experience of 1,357 Caucasian and 1,029 Japanese women with invasive breast carcinoma diagnosed in Hawaii between 1960 and 1979 was examined over a 10-year period as well as by place of birth. Multivariate adjustment by the proportional hazards regression model confirmed that the survival advantage of Japanese women in Hawaii is fully explained by their earlier stage of disease at diagnosis and suggested that, after recognition, the disease progresses at a similar pace in the two races. The survival comparison by place of birth revealed that second generation Hawaii Japanese women had better breast cancer survival rates than Japanese migrants from Japan, even after adjusting for stage, and that for Caucasian women, nativity was not associated with survival. These findings suggest that westernization, genetic constitution, or early life exposures cannot explain the overall or stage-adjusted breast cancer survival patterns observed among Caucasian and Japanese women in Hawaii.