The present nested case-control study was designed to investigate whether the association between carotenoid consumption and risk of breast cancer is related to mammographic density. High breast density as measured by mammography has been reported to be a powerful indicator of increased breast cancer risk. The study included 604 breast cancer cases and 626 cancer-free controls in the Nurses' Health Study for whom circulating carotenoid (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin) levels had been measured and mammograms obtained prospectively. Using a computer-assisted method to determine mammographic density, circulating carotenoids were not found to be associated with mammographic density. However, mammographic density significantly influenced the association between total circulating carotenoids and risk of breast cancer (P heterogeneity = 0.008). Total circulating carotenoid levels were found to be inversely associated with overall breast cancer risk (P trend = 0.01). Among women in the highest third of mammographic density, total circulating carotenoids were associated with a 50% lower risk of breast cancer (odds ratio = 0.5; 95% confidence interval = 0.3 - 0.8). Similarly, among these women, high levels of circulating alpha-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were found to be associated with a significant 40% to 50% reduction in risk of breast cancer (P trend < 0.05). On the other hand, no such inverse association was observed between circulating carotenoids and breast cancer risk among study participants with low mammographic density. The authors conclude that plasma levels of carotenoids may play a role in reducing risk of breast cancer, especially among women with high breast density.

The current study was designed to evaluate the associations between levels of carotenoids, retinol, and tocopherols in the blood with postmenopausal breast cancer risk. Prospective population studies previously have examined such associations, however, the studies only assessed exposure at one point in time, whereas the present study used both baseline and repeated serum measurements. The study included 6% and 1% subsets of participants in the Women's Health Initiative clinical trials. Serum concentrations of α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein + zeaxanthin, retinol, α-tocopherol, and γ-tocopherol were measured at baseline and at years one, three, and six for the 6% sample. In addition, the 1% group was sampled at baseline and at year three. The association of baseline levels and breast cancer risk was estimated by Cox proportional hazards models. Repeated measurements were also analyzed as time-dependent covariates. Of 5,450 women with baseline measurements, 190 incident cases of breast cancer were found during a median follow-up period of eight years. After multivariable adjustment, risk of invasive breast cancer was found to be inversely associated with baseline serum α-carotene concentrations (hazard ratio for highest compared with the lowest third: 0.55; 95% CI: 0.34 - 0.90; P = 0.02). However, the risk of breast cancer was found to be positively associated with baseline lycopene levels (hazard ratio: 1.47; 95% CI: 0.98, 2.22; P = 0.06). Analysis of repeated measurements showed that α-carotene and β-carotene were inversely associated with risk of breast cancer and that γ-tocopherol was associated with increased risk. The authors conclude that this study adds to the evidence of an inverse association of specific carotenoids with breast cancer. They note that the unexpected positive associations observed for lycopene and γ-tocopherol require confirmation.

The present hospital-based case-control study was designed to examine the associations between fruit and vegetable consumption and risk of breast cancer. Four hundred and thirty-eight breast cancer cases in Guangdong, China were matched to 438 controls by age (5-year groupings) and location (rural/urban). Dietary factors were ascertained by interviews using a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after adjusting for various potential confounders. Total overall fruit and vegetable consumption was found to be inversely associated with risk of breast cancer. The odds ratio of the highest fourth relative to the lowest quartile of total fruit consumption was 0.53 (95% CI 0.34-0.82) and for vegetable intake was 0.28 (95% CI 0.18-0.43). Consumption of banana, watermelon/papaya/cantaloupe, dark green leafy vegetables, cruciferous vegetables, carrots, and tomatoes were each significantly associated with lower breast cancer risk. An inverse association with breast cancer risk also was found for intakes of vitamin A, carotene, vitamin C, vitamin E, and fiber. The authors conclude that greater consumption of vegetables and fruits is associated with a lower risk of breast cancer among Chinese women residing in Guangdong.

Some population studies have found a diet high in vegetables to be associated with less likelihood of recurrence in breast cancer survivors. Carotenoids, which are found primarily in vegetables and fruit, are thought to have biological activities that may specifically reduce the progression of breast cancer. The present study was designed to examine the relationship between plasma carotenoids at enrollment and at points in time one, two or three, four, and six years, and breast cancer-free survival. Cases were 3,043 participants in the Women's Healthy Eating and Living Study who had been diagnosed with early-stage breast cancer. The primary end point was time to either a second breast cancer recurrence or a new primary breast cancer. The analysis was adjusted for prognostic and other confounding factors. 508 (16.7%) breast cancer events (recurrence or new primary breast cancer) took place over a median 7.12 years of follow up. Compared with the lowest third, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval, 0.54-0.83). The authors conclude that higher biological exposure to carotenoids was associated with greater likelihood of breast cancer–free survival when assessed over the time frame of the study.

The present study was designed to evaluate the antiproliferative effects of cucurbitacin B against human breast cancer cells. Cucurbitacins are a diverse group of triterpenoid chemicals found in some plants with medicinal properties. The antiproliferative effect of cucurbitacin B was studied in six human breast cancer cell lines representing a mix of breast cancer subtypes. The effective dose inhibiting 50% growth (ED50) was found to be between 10−8 M and 10−7 M for these breast cancer cell lines. The cells underwent rapid morphologic changes after 15 to 20 minutes exposure to cucurbitacin B (5 × 10−7 M), which was associated with disruption of the microtubules and F-actin. Human MDA-MB-231 (ER-, p53 mutated) breast cancer cells were also implanted into the mammary glands of nude mice, who were administered either cucurbitacin B 1.0 mg/kg or a control vehicle intraperitoneally. Mammary tumor volume was found to be reduced by 55 percent in the mice that received cucurbitacin B for six weeks compared to the controls. Pathological assessment found no apparent organ tissue damage. Interestingly, the experimental mice were found to have lower serum glucose levels, consistent with use of cucurbitacin B as an antidiabetic drug in China. This drug appears to be the third in a family of compounds that target cell microtubules, i.e., taxanes (e.g. Taxol), vinca alkaloid (e.g. Vincristine), and now cucurbitacin B. The authors conclude that cucurbitacin B may be a new and effective approach for the treatment of ER-, Her2/neu amplified, and p53 mutant breast cancers.

The present study was designed to evaluate the association between dietary and supplemental intakes of carotenoids and vitamins C and E and the risk of breast cancer according to estrogen receptor (ER) and progesterone receptor (PR) status. The study group included 84,805 postmenopausal women in the Women's Health Initiative Observational Study. During an average follow-up period of 7.6 years, there were 2,879 new cases of invasive breast cancer, of which 2,509 had receptor data. Dietary α-carotene (highest versus lowest quintile: RR = 0.83; 95% CI = 0.70- 0.99; P for trend = 0.019), β-carotene (highest versus lowest quintile: RR = 0.78; 95% CI = 0.66-0.94; P = 0.021), and lycopene (highest versus lowest quintile: RR = 0.85; 95% CI = 0.73-1.00; P = 0.064) were each found to be inversely associated with the risk of ER+/PR+ breast cancer, but not with other breast cancer groups as defined by ER and PR status. Total or supplemental β-carotene and dietary intakes of lutein+zeaxanthin and β-cryptoxanthin were not found to be associated with breast cancers defined by ER and PR status. Vitamin E (regardless of source) and dietary vitamin C were found not to be associated with breast cancer. However, both total (dietary plus supplemental) and supplemental vitamin C intake were found to be weakly positively associated with breast cancer. The authors conclude that dietary intake of certain carotenoids might be differentially associated with risk of invasive breast cancers jointly defined by ER and PR status among postmenopausal women.

The present Chinese population-based case-control study was designed to investigate the association between of breast cancer risk and consumption of vegetables and fruits, as well as related micronutrient intake among women in Shanghai. The study included 1,459 breast cancer cases and 1,556 frequency-matched controls. Dietary habits were determined by in-person interviews. No association was found between breast cancer risk and total overall vegetable intake. However, the risk of breast cancer was found to decline with increasing intake of dark yellow-orange vegetables (adjusted OR in the highest quintile of intake = 0.79, 95% CI = 0.60-0.98), Chinese white turnips (OR = 0.67, 95% CI = 0.53-0.85), and certain dark green vegetables (OR = 0.65, 95% CI = 0.51-0.83). Intake of fruits, except watermelons and apples, was also found to be inversely associated with risk of breast cancer risk. This authors conclude that high consumption of certain vegetables and fruits may be associated with a reduced risk of breast cancer.