Abstract: 2019-06-20¶
Contents¶
Perspective¶
Case Studies in Social Medicine: Misrecognition and Critical Consciousness — An 18-Month-Old Boy with Pneumonia and Chronic Malnutrition¶
An 18-month-old boy in La Soledad, Mexico, presents with pneumonia, to which he was predisposed by malnutrition. When nutrition education and food-production efforts fail, a physician and a community collaborative work to elucidate the deeper roots of the problem.
Collateral Benefits of Preventive Chemotherapy — Expanding the War on Neglected Tropical Diseases¶
[preventive chemotherapy]
- 7 [neglected tropical disease]s
- 3 soil-transmitted helminth infxn
- ascariasis
- trichuriasis
- hookworm
- schistosomiasis
- lymphatic filariasis
- onchocerciasis
- trachoma
- 3 soil-transmitted helminth infxn
The collateral and extended effects of [preventive chemotherapy], many of which were unanticipated, have reduced disease burdens and saved lives on a scale that appears to have exceeded the intended impact on seven [neglected tropical disease]s (NTDs) — the three major soil-transmitted helminth infections (ascariasis, trichuriasis, and hookworm infection), schistosomiasis, lymphatic filariasis, onchocerciasis, and trachoma.
Has the Genome Granted Our Wish Yet?¶
Interpretation of [polygenic risk score]s will someday become an accepted part of clinical practice — but not just yet. It is, however, time to evaluate these scores in studies that assess clinical utility, benefits and costs, and scalable risk-communication methods.
Original Articles¶
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer¶
BACKGROUND
The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known.
METHODS
We performed a prospective trial involving 9427 women with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger.
RESULTS
The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%).
CONCLUSIONS
Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.)