Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed, refractory, or ineligible, to an IMiD (Immunomodulatory Drug), with measurable disease and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (51%) including >=partial response in 69 (38%). The median overall survival and event free survival from T0 were 9 and 5 months respectively. This study confirms the poor outcome once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.

• Lenalidomide-bortezomibdexamethasone resulted in partial response or better in nearly two-thirds of relapsed/ refractory myeloma patients.• The regimen had substantial activity despite high rates of prior bortezomib/thalidomide and regardless of poor prognostic characteristics.In this prospective, multicenter, phase 2 study, 64 patients with relapsed or relapsed and refractory multiple myeloma (MM) received up to 8 21-day cycles of bortezomib 1.0 mg/m 2 (days 1, 4, 8, and 11), lenalidomide 15 mg/day (days 1-14), and dexamethasone 40/20 mg/day (cycles 1-4) and 20/10 mg/day (cycles 5-8) (days of/after bortezomib dosing). Responding patients could receive maintenance therapy. Median age was 65 years; 66% were male, 58% had relapsed and 42% had relapsed and refractory MM, and 53%, 75%, and 6% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Forty-eight of 64 patients (75%; 90% confidence interval, 65-84) were alive without progressive disease at 6 months (primary end point). The rate of partial response or better was 64%; median duration of response was 8.7 months. Median progression-free and overall survivals were 9.5 and 30 months, respectively (median follow-up: 44 months). Common treatment-related toxicities included sensory neuropathy (53%), fatigue (50%), and neutropenia (42%); common grade 3/4 treatment-related toxicities included neutropenia (30%), thrombocytopenia (22%), and lymphopenia (11%). Grade 3 motor neuropathy was reported in 2 patients. Lenalidomidebortezomib-dexamethasone appears effective and tolerable in patients with relapsed or relapsed and refractory MM, demonstrating substantial activity among patients with diverse prior therapies and adverse prognostic characteristics. This trial is registered with

Three methods of estimating group and individual dietary consumption have been developed and assessed in a case-control study of diet and breast cancer. The methods comprised a 24-hour recall, a detailed quantitative diet history directed to the most recent two-month period and the two-month period six months before, and a four-day diet diary. There is a high degree of correlation between the estimates of food consumption for the controls using each of the methods. The highest estimate was obtained from the diet history, with a slightly higher estimate in the period six months before than the current period, while the lowest is found in the 24-hour recall. The latter corresponds with the same method in a Nutrition Canada Survey. It is concluded that all methods ara applicable to case-control studies, but the diet history is preferred when current food intake may be influenced by a disease.

A case-control study has been conducted in four areas of Canada in which 400 cases of breast cancer matched by age and marital status with neighborhood controls were administered medical and dietary questionnaires. The study is suggestive of an increased risk of breast cancer in post-menopausal women with younger age at menarche and an increased risk with delay of age at natural menopause. No protective effect of early age at first pregnancy was demonstrated in either pre- or post-menopausal women. An increased frequency of pregnancies of four months duration or less was found in cases compared to controls and a greater frequency in pre-menopausal cases compared to controls of a history of irregular menstrual periods. In pre-menopausal women no association has been found between increased height and weight as risk factors for breast cancer. For post-menopausal women, however, a weak association with increased height has been found, while a strong association with increased weight both at the time of menopause and the 12 months preceding diagnosis has ben confirmed.