The prognostic value of Ki67 in systemically untreated patients with node-negative breast cancer.

AIM: To evaluate the utility of Ki67 as a prognostic marker in a series of patients with node-negative breast cancer untreated with adjuvant systemic therapy. METHODS: The cohort consisted of 203 cases treated with breast conserving surgery and radiation only; median follow-up was 183 months (range 156-277 months). An immunohistochemical panel of oestrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK)5/6 and Ki67 and human epidermal growth factor 2 in situ hybridization (HER2-ISH) was performed on the tumour samples. Ki67 scores were evaluable in 193/203 patients (95.1%). The primary outcome was breast cancer specific survival (BCSS). RESULTS: Of the cohort, 29 (14.2%) died of breast cancer. A cut off of 10% separated tumours into a 'Ki67-low' (n=70) or 'Ki67-high' group (n=123). The breast cancer specific survival was 97.1% and 77.6% for Ki67-low and Ki67-high groups, respectively. Univariate analysis showed that in this lymph node-negative cohort, the predictors for BCSS were tumour size, Ki67, LVI, age and histological grade 3. Multivariable analysis showed that Ki67 index and lymphovascular space invasion were independent predictors of breast cancer death. To examine the utility of Ki67 in assignment of immunohistochemically molecular subtypes, cases were assigned into Luminal A (ER-positive, HER2-negative, Ki67 ≤14%), Luminal B (ER-positive, HER2-negative, Ki67 >14%) and triple negative (ER/PR-negative and HER2-negative, any Ki67). The 15-year breast cancer specific survival was 91.7%, 79.4% and 75.8%, respectively. CONCLUSIONS: A statistically significant difference in breast cancer specific survival is seen in groups defined using Ki67 and receptor status, whereas histological grading was not a significant predictor of survival. Ki67 immunostaining provides prognostic information beyond traditionally assessed clinicopathological variables.

Burning daylight: balancing vitamin D requirements with sensible sun exposure.

OBJECTIVE: To examine the feasibility of balancing sunlight exposure to meet vitamin D requirements with sun protection guidelines. DESIGN AND SETTING: We used standard erythemal dose and Ultraviolet Index (UVI) data for 1 June 1996 to 30 December 2005 for seven Australian cities to estimate duration of sun exposure required for fair-skinned individuals to synthesise 1000 IU (25 µg) of vitamin D, with 11% and 17% body exposure, for each season and hour of the day. Periods were classified according to whether the UVI was < 3 or ≥ 3 (when sun protection measures are recommended), and whether required duration of exposure was ≤ 30 min, 31-60 min, or > 60 min. MAIN OUTCOME MEASURE: Duration of sunlight exposure required to achieve 1000 IU of vitamin D synthesis. RESULTS: Duration of sunlight exposure required to synthesise 1000 IU of vitamin D varied by time of day, season and city. Although peak UVI periods are typically promoted as between 10 am and 3 pm, UVI was often ≥ 3 before 10 am or after 3 pm. When the UVI was < 3, there were few opportunities to synthesise 1000 IU of vitamin D within 30 min, with either 11% or 17% body exposure. CONCLUSION: There is a delicate line between balancing the beneficial effects of sunlight exposure while avoiding its damaging effects. Physiological and geographical factors may reduce vitamin D synthesis, and supplementation may be necessary to achieve adequate vitamin D status for individuals at risk of deficiency.