Macadamia nut effects on cardiometabolic risk factors: a randomised trial.

We sought to examine the effects of daily consumption of macadamia nuts on body weight and composition, plasma lipids and glycaemic parameters in a free-living environment in overweight and obese adults at elevated cardiometabolic risk. Utilising a randomised cross-over design, thirty-five adults with abdominal obesity consumed their usual diet plus macadamia nuts (~15 % of daily calories) for 8 weeks (intervention) and their usual diet without nuts for 8 weeks (control), with a 2-week washout. Body composition was determined by bioelectrical impedance; dietary intake was assessed with 24-h dietary recalls. Consumption of macadamia nuts led to increased total fat and MUFA intake while SFA intake was unaltered. With mixed model regression analysis, no significant changes in mean weight, BMI, waist circumference, percent body fat or glycaemic parameters, and non-significant reductions in plasma total cholesterol of 2⋅1 % (-4⋅3 mg/dl; 95 % CI -14⋅8, 6⋅1) and low-density lipoprotein (LDL-C) of 4 % (-4⋅7 mg/dl; 95 % CI -14⋅3, 4⋅8) were observed. Cholesterol-lowering effects were modified by adiposity: greater lipid lowering occurred in those with overweight v. obesity, and in those with less than the median percent body fat. Daily consumption of macadamia nuts does not lead to gains in weight or body fat under free-living conditions in overweight or obese adults; non-significant cholesterol lowering occurred without altering saturated fat intake of similar magnitude to cholesterol lowering seen with other nuts. Clinical Trial Registry Number and Website: NCT03801837 https://clinicaltrials.gov/ct2/show/NCT03801837?term = macadamia + nut&draw = 2&rank = 1.

Evaluation of hereditary risk in a mammography population.

PURPOSE: BRCA1 and BRCA2 mutations significantly increase a women's lifetime risk of breast and ovarian cancer. Because several management options have shown promise in decreasing morbidity and mortality for these women, identifying potential mutation carriers is increasingly important. We have developed a large-scale method to collect family histories in a population of unaffected women presenting for mammography. We then applied current risk-assessment models to determine the prevalence of women at risk for hereditary breast and ovarian cancer. MATERIALS AND METHODS: We performed a retrospective review of family histories using data collected on all unaffected women presenting for mammography over a 14-week period. The Claus, Myriad II, and Hartmann models for hereditary risk assessment were applied to the survey results. RESULTS: The questionnaire was completed by 5736 women, 695 of whom were excluded because of a personal history of breast or ovarian cancer. Family histories of the remaining 5041 women were evaluated. Totals of 5.9%, 5.2%, and 3.3% of patients, respectively, met criteria for increased risk according to the Hartmann, Myriad II, and Claus models, corresponding to 3.5, 3.1, and 1.9 patients per day. Although 9.2% of patients met criteria for >/=1 model, only 1.4% met criteria for all 3. CONCLUSIONS: Application of available models to a screening population classifies a larger than expected number of women at high risk for a BRCA1 or BRCA2 mutation. New approaches to risk assessment and counseling are needed to apply our knowledge of hereditary risk to a broad population in a practical manner.

A comparison of sentinel node biopsy before and after neoadjuvant chemotherapy: timing is important.

BACKGROUND: Because neoadjuvant chemotherapy is being used more frequently, the optimal timing of sentinel node biopsy (SNB) remains controversial. We previously evaluated the predictive value of SNB before neoadjuvant chemotherapy in clinically node-negative breast cancer. Our identification rate of the sentinel node among 52 patients before chemotherapy with a mean tumor size of 4 cm was 100%. In this study, we compared the identification rates of SNB before and after neoadjuvant chemotherapy and evaluated the false-negative rate of SNB after chemotherapy. METHODS: A retrospective institutional database review identified 36 women who underwent SNB after neoadjuvant chemotherapy for breast cancer from 1999 to 2004. The initial clinical tumor size and lymph node status, SNB pathology, axillary lymph node dissection pathology, and residual pathologic tumor size were reviewed. RESULTS: Sixteen of 36 patients had a clinically negative axilla before neoadjuvant therapy. SNB after neoadjuvant therapy was successful in 29 patients (80.6%), although 7 patients did not map (19.4%). Six of the 7 patients who failed to map had a clinically positive axilla initially. Axillary disease was found in 6 of 7 of these patients at dissection (85.7%). Of the 29 patients who mapped successfully, 13 (45%) were SNB negative, and 16 (55%) were SNB positive. Of the 13 SNB-negative patients, 2 had a positive axillary lymph node dissection, yielding a false-negative rate of 11%. Thirteen patients who mapped had a clinically positive axilla before therapy (45%). Of the 11 patients with true-negative SNBs, 7 (64%) were clinically node negative at presentation. The initial tumor sizes on examination ranged from 2 to 9 cm (mean, 5.0 cm), and residual pathologic tumor sizes ranged from 0 to 6 cm (mean, 1.8 cm). Failure to map correlated with a clinically positive axilla at presentation (100% vs 45%) but did not correlate with initial tumor size. CONCLUSIONS: Sentinel node identification rates are significantly better when mapping is performed before neoadjuvant chemotherapy (100% vs 80.6%), with failure to map correlated with clinically positive nodal disease at presentation and residual disease at axillary lymph node dissection. Among patients who map successfully after chemotherapy, the false-negative rate is high (11%). Given these findings, we currently recommend SNB before neoadjuvant chemotherapy for clinically node-negative patients, and raise concerns about the use of SNB after neoadjuvant therapy in patients with an initially clinically positive axilla.

Breast cancer treatment in older women.

This article presents the author's current approaches to the management of breast cancer in older women, with emphasis on clinical and surgical treatment of the disease in this population. There are controversies surrounding the management of breast cancer in this population regarding adjuvant therapy, radiation therapy and surgical options. We endeavor to address these issues in the article.

Genistein inhibits tamoxifen effects on cell proliferation and cell cycle arrest in T47D breast cancer cells.

Tamoxifen is an antiestrogen used in the treatment of estrogen receptor-positive breast cancer in postmenopausal women. It functions by competitively inhibiting the estrogen receptor and inducing apoptosis and G1 cell cycle arrest. Genistein is a soy phytoestrogen that inhibits breast cancer cell growth in vitro at doses of 10 microM or above. At lower doses genistein may stimulate cell growth and entry into the cell cycle. We hypothesized that treatment with low-dose genistein would reverse the inhibitory effects of tamoxifen in estrogen-receptor-positive breast cancer cells. Cell cycle kinetics and cell proliferation in T47-D human breast cancer cells were examined after exposure to genistein and tamoxifen in a low-estrogen environment designed to mimic a post-menopausal state. Cell proliferation was assessed by a colorimetric assay. Cell cycle kinetics were determined by flow cytometry. Tamoxifen caused G1 arrest and a decrease in proliferation. Genistein reversed the inhibitory effects of tamoxifen on both proliferation and G1 arrest. Thus low-dose genistein was able to inhibit the therapeutic effects of tamoxifen in this postmenopausal model of breast cancer.

Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion?

BACKGROUND: Because the implications of micrometastases found on sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCISM) are largely unknown, we wished to determine if SNB pathology predicted recurrence risk in DCIS/DCISM. METHODS: Retrospective chart review identified patients with DCIS/DCISM who underwent SNB. SNB findings and all local and distant recurrences were determined. RESULTS: A total of 322 patients underwent SNB for DCIS/DCISM. There were 13 local recurrences (4.0%) and 1 (.03%) distant recurrence at a median follow-up of 47.9 months (range 0 to 110.6), 12 in patients with negative SNBs; 1 patient had a positive SNB. There were 4 recurrences after mastectomy and 9 after lumpectomy. In 29 patients with positive SNBs, there was only 1 recurrence (3.4%). CONCLUSIONS: Positive SNBs in patients with DCIS or DCISM are not associated with higher risk of local or distant recurrence. Other features of DCIS and DCISM may be important in predicting recurrence risk.

Breast cancer diagnosis in women < or = 40 versus 50 to 60 years: increasing size and stage disparity compared with older women over time.

BACKGROUND: Women < or = 40 years account for 5% of new breast cancer diagnoses. Although there is increased awareness of genetic and other breast cancer risk factors, it is not clear whether this has resulted in earlier diagnosis in young women. METHODS: A database review identified 8892 women treated for breast cancer from 1980 to 2002. We compared 925 women aged < or = 40 years with 2362 women aged 50 to 60 years. The mean and median tumor size and lymph node status were determined for each group. RESULTS: There were significant differences in tumor size and lymph node status in younger versus older women. From 1980 to the mid 1990s, tumor size and nodal status did not differ. Since the mid 1990s, tumor size has decreased more rapidly for women aged 50 to 60 years than for those < or = 40 years. In 1998 to 2002, the mean tumor size reached a plateau of 1.8 cm in women 50 to 60 years, compared with a plateau of 2.4 cm in women < or = 40 years (P < .001). The median tumor size in 1998 to 2002 was 1.4 cm in women 50 to 60 years compared with 1.9 cm in women < or = 40 years (P < .001). Lymph node status was also significantly different during 1998 to 2002: 23.9% positive in women 50 to 60 years versus 35.2% in women < or = 40 years (P < .001). CONCLUSIONS: Since the 1980s, women aged 50 to 60 years have enjoyed a greater decrease in tumor size and percentage with positive nodes. These data could be the result of ineffective screening of younger women or of more aggressive tumor biology. Further study is required to determine whether more effective identification and screening of young, high-risk women can result in earlier detection.

Prevalence of hereditary breast/ovarian carcinoma risk in patients with a personal history of breast or ovarian carcinoma in a mammography population.

BACKGROUND: Identifying BRCA1 and BRCA2 mutation carriers is increasingly important as new management options show promise in decreasing morbidity and mortality in these women. The authors sought to determine the prevalence of family histories suggestive of a hereditary breast carcinoma syndrome in a cohort of patients with a personal history of breast and/or ovarian carcinoma presenting for mammography. METHODS: The authors reviewed the family histories of all women with a history of breast or ovarian carcinoma presenting for mammography over a 37-week period. Using the Myriad model, the authors evaluated the prevalence of family histories with a > or = 10% risk of a BRCA1 or BRCA2 mutation. RESULTS: During the period of the current study, 14,597 women completed a family history questionnaire. Of these women, 1764 had a personal history of breast or ovarian carcinoma, 86.6% had unilateral breast carcinoma, 4.6% had bilateral breast carcinoma, 8.2% had ovarian carcinoma, and 0.5% had both breast and ovarian carcinoma. Overall, 20.6% met the criteria for a > or = 10% risk of mutation according to the Myriad model. This incidence was higher among Ashkenazi women (47.3%) and among patients with a personal history of ovarian carcinoma (35.9%). CONCLUSIONS: Application of the Myriad model to women with a personal history of breast and ovarian carcinoma suggested that approximately 1 in 5 of these women (20.6%) will have family histories suspicious for a genetic mutation. This risk was higher for Ashkenazi women and for those with a personal history of ovarian carcinoma. This prevalence was considerably higher than the rate reported among women with no personal history of cancer, and has significant implications for their management, as well as for the capacity for risk assessment and testing.