1. Genes to predict recurrence of breast cancer.
   
2. Secondary surgical cytoreduction for advanced ovarian carcinoma.
   
3. Breast cancer risk associated with being treated for infertility.
   

Reproductive Medicine

4. Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization.
   

1. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. It was tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer.

Reference

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004 351:2817-2826.

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2. Secondary surgical cytoreduction for advanced ovarian carcinoma.

The effect was evaluated of adding secondary cytoreductive surgery to postoperative chemotherapy on progression-free survival and overall survival among patients who had advanced ovarian cancer and residual tumor exceeding 1 cm in diameter after primary surgery. Women were enrolled within six weeks after primary surgery. If, after three cycles of postoperative paclitaxel plus cisplatin, a patient had no evidence of progressive disease, she was randomly assigned to undergo secondary cytoreductive surgery followed by three more cycles of chemotherapy or three more cycles of chemotherapy alone. 550 women could be enrolled. After completing three cycles of postoperative chemotherapy, 216 eligible patients were randomly assigned to receive secondary surgical cytoreduction followed by chemotherapy and 208 to receive chemotherapy alone. Surgery was declined by or medically contraindicated in 15 patients who were assigned to secondary surgery (7 percent). As of March 2003, 296 patients had died and 82 had progressive disease. The likelihood of progression-free survival in the group assigned to secondary surgery plus chemotherapy, as compared with the chemotherapy-alone group, was 1.07 (95 percent confidence interval, 0.87 to 1.31; P=0.54), and the relative risk of death was 0.99 (95 percent confidence interval, 0.79 to 1.24; P=0.92). For patients with advanced ovarian carcinoma in whom primary cytoreductive surgery was considered to be maximal, the addition of secondary cytoreductive surgery to postoperative chemotherapy with paclitaxel plus cisplatin does not improve progression-free survival or overall survival.

Reference

Rose PG, Nerenstone S, Brady MF, Clarke-Pearson D, Olt G, Rubin SC, Moore DH, Small JM; Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med. 2004 Dec 9;351(24):2489-97.

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3. Breast cancer risk associated with being treated for infertility.

The use of fertility drugs (FDs) is steadily increasing in Western countries and concern has been raised as to the possible impact of fertility treatments on breast cancer risk. This association was analysed in the French E3N study. In this prospective cohort, data on treatment against infertility, duration and time of administration were collected at entry through self-administered questionnaires. Cox regression analysis was used to estimate adjusted relative risks (RRs). Among the 92 555 women from the study population, 6602 women were treated for infertility. During the 10 year follow-up period, 2571 cases of primary invasive breast cancer were diagnosed (183 in treated women). Our study showed no overall significant association between breast cancer risk and treatment for infertility (RR = 0.95, confidence interval 0.82-1.11), after surgery or FDs, and whatever the type, the duration of use and the age at first use of FDs. However, infertility treatment was associated with an increased risk, of borderline significance, of breast cancer among women with a family history of breast cancer. This last result had limited statistical power. Our study provides evidence that treatment for infertility does not influence breast cancer risk overall. An interaction with a familial history of breast cancer is possible but should be investigated further.

Reference

Gauthier E, Paoletti X, Clavel-Chapelon F; E3N group. INSERM, equipe E3N, Breast cancer risk associated with being treated for infertility: results from the French E3N cohort study. Hum Reprod. 2004 Oct;19(10):2216-21. Epub 2004 Jul 22.

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4. Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization.

The risks of premature birth and perinatal death are increased after in vitro fertilization. These risks are mainly due to the high incidence of multiple births, which relates to the number of embryos transferred. A randomized, multicenter trial was performed to assess the equivalence of two approaches to in vitro fertilization with respect to the rates of pregnancy that result in at least one live birth and to compare associated rates of multiple gestation. Women less than 36 years of age who had at least two good-quality embryos were randomly assigned either to undergo transfer of a single fresh embryo and, if there was no live birth, subsequent transfer of a single frozen-and-thawed embryo, or to undergo a single transfer of two fresh embryos. Equivalence was defined as a difference of no more than 10 percentage points in the rates of pregnancy resulting in at least one live birth. Pregnancy resulting in at least one live birth occurred in 142 of 331 women (42.9 percent) in the double-embryo-transfer group as compared with 128 of 330 women (38.8 percent) in the single-embryo-transfer group (difference, 4.1 percentage points; 95 percent confidence interval, -3.4 to 11.6 percentage points); rates of multiple births were 33.1 percent and 0.8 percent, respectively (P<0.001). These results do not demonstrate equivalence of the two approaches in rates of live births, but they do indicate that any reduction in the rate of live births with the transfer of single embryos is unlikely to exceed 11.6 percentage points. In women under 36 years of age, transferring one fresh embryo and then, if needed, one frozen-and-thawed embryo dramatically reduces the rate of multiple births while achieving a rate of live births that is not substantially lower than the rate that is achievable with a double-embryo transfer.

Reference

Thurin A, Hausken J, Hillensjo T, Jablonowska B, Pinborg A, Strandell A, Bergh C. Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. N Engl J Med. 2004 Dec 2;351(23):2392-402.

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