US Preventive Services Task Force (USPSTF) и American Society of Clinical Oncology (ASCO) выпустили обновленные руководства по использованию эндокринной терапии в качестве первичной профилактики у женщин с высоким риском развития рака молочной железы.
Оба руководства теперь рекомендуют назначение селективных модуляторов рецепторов эстрогена (тамоксифен, ралоксифен, торемифен и др.) в сочетании с ингибиторами ароматазы (летрозол, анастрозол и эксеместан) женщинам в постменопазе с высоким риском рака молочной железы. Именно использование ингибиторов ароматазы является новым дополнением к руководству USPSTF.
Данные поправки были внесены в руководства на основании систематического обзора двух исследований женщин в постменопаузе с высоким риском развития рака молочной железы. Обзор показал, что своевременная первичная эндокринная профилактика способствует приблизительно 50-процентному снижению риска развития инвазивного рака молочной железы по сравнению с плацебо.
JAMA. 2019 Sep 3;322(9):857-867. doi: 10.1001/jama.2019.11885.
Nelson HD et al
Medications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects.
To update the 2013 US Preventive Services Task Force systematic review on medications to reduce risk of primary (first diagnosis) invasive breast cancer in women.
Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE, and MEDLINE (January 1, 2013, to February 1, 2019); manual review of reference lists.
Discriminatory accuracy studies of breast cancer risk assessment methods; randomized clinical trials of tamoxifen, raloxifene, and aromatase inhibitors for primary breast cancer prevention; studies of medication adverse effects.
DATA EXTRACTION AND SYNTHESIS:
Investigators abstracted data on methods, participant characteristics, eligibility criteria, outcome ascertainment, and follow-up. Results of individual trials were combined by using a profile likelihood random-effects model.
MAIN OUTCOMES AND MEASURES:
Probability of breast cancer in individuals (area under the receiver operating characteristic curve [AUC]); incidence of breast cancer, fractures, thromboembolic events, coronary heart disease events, stroke, endometrial cancer, and cataracts; and mortality.
A total of 46 studies (82 articles [>5 million participants]) were included. Eighteen risk assessment methods in 25 studies reported low accuracy in predicting the probability of breast cancer in individuals (AUC, 0.55-0.65). In placebo-controlled trials, tamoxifen (risk ratio [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials [n = 28 421]), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials [n = 17 806]), and the aromatase inhibitors exemestane and anastrozole (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials [n = 8424]) were associated with a lower incidence of invasive breast cancer. Risk for invasive breast cancer was higher for raloxifene than tamoxifen in 1 trial after long-term follow-up (RR, 1.24 [95% CI, 1.05-1.47]; n = 19 747). Raloxifene was associated with lower risk for vertebral fractures (RR, 0.61 [95% CI, 0.53-0.73]; 2 trials [n = 16 929]) and tamoxifen was associated with lower risk for nonvertebral fractures (RR, 0.66 [95% CI, 0.45-0.98]; 1 trial [n = 13 388]) compared with placebo. Tamoxifen and raloxifene were associated with increased thromboembolic events compared with placebo; tamoxifen was associated with more events than raloxifene. Tamoxifen was associated with higher risk of endometrial cancer and cataracts compared with placebo. Symptomatic effects (eg, vasomotor, musculoskeletal) varied by medication.
CONCLUSIONS AND RELEVANCE:
Tamoxifen, raloxifene, and aromatase inhibitors were associated with lower risk of primary invasive breast cancer in women but also were associated with adverse effects that differed between medications. Risk stratification methods to identify patients with increased breast cancer risk demonstrated low accuracy.
Visvanathan K et al
To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction.
An Expert Panel conducted targeted systematic literature reviews to identify new studies.
A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor-positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update.
In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines.
US Preventive Services Task Force, Owens DK et al
Breast cancer is the most common nonskin cancer among women in the United States and the second leading cause of cancer death. The median age at diagnosis is 62 years, and an estimated 1 in 8 women will develop breast cancer at some point in their lifetime. African American women are more likely to die of breast cancer compared with women of other races.
To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on medications for risk reduction of primary breast cancer.
The USPSTF reviewed evidence on the accuracy of risk assessment methods to identify women who could benefit from risk-reducing medications for breast cancer, as well as evidence on the effectiveness, adverse effects, and subgroup variations of these medications. The USPSTF reviewed evidence from randomized trials, observational studies, and diagnostic accuracy studies of risk stratification models in women without preexisting breast cancer or ductal carcinoma in situ.
The USPSTF found convincing evidence that risk assessment tools can predict the number of cases of breast cancer expected to develop in a population. However, these risk assessment tools perform modestly at best in discriminating between individual women who will or will not develop breast cancer. The USPSTF found convincing evidence that risk-reducing medications (tamoxifen, raloxifene, or aromatase inhibitors) provide at least a moderate benefit in reducing risk for invasive estrogen receptor-positive breast cancer in postmenopausal women at increased risk for breast cancer. The USPSTF found that the benefits of taking tamoxifen, raloxifene, and aromatase inhibitors to reduce risk for breast cancer are no greater than small in women not at increased risk for the disease. The USPSTF found convincing evidence that tamoxifen and raloxifene and adequate evidence that aromatase inhibitors are associated with small to moderate harms. Overall, the USPSTF determined that the net benefit of taking medications to reduce risk of breast cancer is larger in women who have a greater risk for developing breast cancer.
CONCLUSIONS AND RECOMMENDATION:
The USPSTF recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women who are at increased risk for breast cancer and at low risk for adverse medication effects. (B recommendation) The USPSTF recommends against the routine use of risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, in women who are not at increased risk for breast cancer. (D recommendation) This recommendation applies to asymptomatic women 35 years and older, including women with previous benign breast lesions on biopsy (such as atypical ductal or lobular hyperplasia and lobular carcinoma in situ). This recommendation does not apply to women who have a current or previous diagnosis of breast cancer or ductal carcinoma in situ.