Abstract
Introduction
Our goal in selecting these top articles about breast health in 2018 was to help identify literature that may change the clinical practice of women's health for internists. We identified articles by reviewing the high-impact medical and women's health journals, national guidelines, ACP JournalWise and NEJM Journal Watch. We have chosen to highlight new information about risk factors for the development of breast cancer (especially in breast cancer survivors), new information about breast cancer diagnosis, and finally, data about indications for chemotherapy use.
Risk Factors for Breast Cancer
More insight into the cancer risks of oral contraceptives
Michels KA, Pfeiffer RM, Brinton LA, Trabert B. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast and colorectal cancers. JAMA Oncol 2018;4:516–521.
What we know
Oral contraceptive (OC) use is common in reproductive-age women, but despite extensive study, uncertainties remain regarding the association between the use of hormonal contraception and the risk of breast cancer. Inconsistent findings from no elevation to an elevation of 20%–30% risk have been reported. Last year a study, reported in the NEJM, reported an increased risk of breast cancer with current OC use after as little as 5 years of use and remaining for at least 5 years after discontinuation of OC. This was a much stronger association of breast cancer with OC use than had previously been reported and renewed concerns about the association between OC use and breast cancer. This study addresses the associations between duration of OC use and a variety of cancers and reviewed their modification by family history and lifestyle factors.
Study results
Data from the NIH-AARP Diet and Health Study cohort were analyzed. This is a large, prospective study of 3.5 million women enrolled between the ages of 50 and 71. Information on the duration of OC use, demographic characteristics, family history of cancer, and lifestyle factors (smoking, weight, alcohol use, and exercise) was collected as baseline data before any cancer diagnosis was made. Participants were observed from enrollment until the first date of diagnosis of cancer, death, or end of study. Associations between OC use and each cancer of interest were calculated and then stratified by family history and lifestyle factors. Forty percent of the cohort were OC users: 34,866 women used OCs for 1–4 years; 24,564 women used OCs for 5–9 years; and 18,962 women used OCs for more than 10 years (long-term use). Long-term use reduced ovarian cancer risk by 40% (hazard ratio [HR] 0.60, p for trend <0.001). Risk reduction was noted with increasing use among all lifestyle modifiers. Long-term use reduced endometrial cancer risk by 34% (HR 0.66, p for trend <0.001). The association was strongest among smokers and was not associated with a reduction in women with body mass indexes of 25 or less. There was no statistically significant association noted between OC use and breast cancer. Only long-term users who also smoked had a significantly increased breast cancer risk of 21% (HR 1.21, 95% confidence interval [CI] 1.01–1.44). Family history was not predictive of OC use and breast cancer risk. There was no association between OC use and colon cancer.
What this changes or adds
This study confirms the previously noted reduction in ovarian and endometrial cancer in long-term users of OCs. There was no reduction in colon cancer risk even in long-term users of OCs. Most importantly, the null association between even long-term OC use and breast cancer, even in women with a family history of breast cancer, in this large, well-done cohort study is reassuring for both patients and providers. The one exception to this was an increased breast cancer risk in long-term users who are also smokers. This study helps to inform our counseling of patients about the risks and benefits of OC use and reminds us that all risks and benefits must be included in the counseling.
No increased risk of breast cancer after pregnancy in breast cancer survivors
Lambertini M, Kroman N, Ameye L, et al. Long-term safety of pregnancy following breast cancer according to estrogen receptor status. J Natl Cancer Inst 2018:110:426–429.
What we know
The recurrence rate of breast cancer in estrogen receptor-positive breast cancer patients after pregnancy remains uncertain. Physicians and patients remain concerned about the safety of pregnancy in these patients as the estrogen exposure of pregnancy is hypothesized to be tumor promoting. Previous studies with short-term follow-up suggested no increased risk of recurrence. This study reports survival analysis at median follow-up of 7.2 years after pregnancy.
Study results
The authors conducted a multicenter, case–control study of 333 breast cancer survivors matched to 874 nonpregnant breast cancer survivors with similar patient characteristics. The primary outcome was disease-free survival (DFS) in Estrogen Receptor (ER)-positive patients. Overall survival (OS) was a secondary endpoint. There was no difference in DFS between groups after a median of 7.2 years of follow-up. The HR for ER-positive pregnant survivors was 0.94 (95% CI 0.70–1.26, p = 0.68) and for ER-negative pregnant survivors was 0.75 (95% CI 0.53–1.06, p = 0.10). No OS difference was noted in the ER-positive patients with an HR of 0.84 (95% CI 0.60–1.18, p = 0.32).
What this study changes or adds
This study provides reassurance about the long-term safety of pregnancy in breast cancer survivors, even those with ER-positive disease. The limitations of this study include that it was retrospective, there was a paucity of HER2 status for the majority of patients, and the possibility that some pregnant patients may have had additional screening before considering pregnancy. Nonetheless, these results provide helpful information to both patients and counseling physicians regarding the safety of pregnancy after breast cancer diagnosis and treatment.
Can BRCA1 patients safely use hormone therapy after oophorectomy?
Kotsopoulos J, Gronwald J, Karlan BY, et al. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncol 2018;4:1059–1065.
What we know
Women with known BRCA1 mutations increasingly are choosing to undergo bilateral oophorectomy to prevent ovarian cancer thus inducing early menopause and increasing the risks of severe vasomotor symptoms as well as osteoporosis, heart disease, and cognitive decline. Hormone therapy (HT) is often prescribed after surgical menopause to BRCA1 patients with no history of breast cancer, but the long-term impact of HT in subsequent breast cancer development in this high-risk cohort remains unclear, causing uncertainly in decision-making for both patients and providers.
The study
The authors conducted a prospective, longitudinal cohort study of women diagnosed with BRCA1 and BRCA2 gene mutations with a mean follow-up of 7.6 years. Patients without any personal history of breast cancer (PHBC) who underwent elective oophorectomy were eligible for the study. Participants were surveyed every 2 years regarding HT use and breast cancer diagnosis. A total of 872 BRCA mutation carriers were enrolled; 377 women elected to receive HT and 495 received no HT. Mean age of participants was 43.4 years and mean follow-up was 7.6 years. Overall, HT use after oophorectomy was not associated with an increased cancer risk. The HR for breast cancer development was 0.97 (95% CI 0.62–1.52, p = 0.89) for ever use of any type of HT versus no use. As has been seen previously, the cumulative risk for breast cancer development for estrogen alone (12%) versus combination therapy (22%) was different (p = 0.04).
What this study changes or adds
These findings are reassuring that the use of estrogen supplementation for symptom management and long-term health after prophylactic oophorectomy in BRCA mutation carriers does not increase the risk of breast cancer. The effects of combination HT on breast cancer risk warrant further study.
Breast Cancer Diagnosis
Digital breast tomosynthesis plus digital mammography for breast cancer screening
Pattacini P, Nitrosi A, Giorgi Rossi P, et al. Digital mammography versus digital mammography plus tomosynthesis for breast cancer screening: The Reggio Emilia Tomosynthesis randomized trial. Radiology 2018;288:375–385.
What we know
Digital breast tomosynthesis (DBT), or three-dimensional mammography, has been shown in multiple studies to increase cancer detection rates when performed in addition to conventional two-dimensional mammography for breast cancer screening. Major guideline organizations in the United States and in other countries have not yet incorporated DBT into standard screening guidelines, however, in part, because the balance between the potential benefits and harms (such as false positives, overdiagnosis, and others) and the impact of this modality on overall prognosis and cancer-related morbidity/mortality remain uncertain. Despite this lack of clarity, DBT has been implemented in many screening facilities within the United States. The goal of this randomized trial was to compare DBT+digital mammography (DM) to DM alone for breast cancer screening in a population of women in northern Italy. In this report of a preplanned interim analysis of an ongoing trial, authors compare cancer detection rates and recall rates for the two study arms.
Study results
Women ages 45–70 who previously participated in regular mammogram screening through a program in northern Italy were randomized to DBT+DM (9777 women) or DM alone (9783 women). While recall rates were similar in both arms (3.5%), the cancer detection rate was higher in the DBT+DM arm than the DM arm (8.6 per 1000 vs. 4.5 per 1000), with the gain in detection over mammogram alone being higher than gains reported in previous observational studies. Notably, the increased detection rate was observed for all cancers except large (>20 mm) and late (grade 3) cancers. DBT+DM also detected more Ductal Carcinoma in Situ (DCIS) (additional 1 case per 1000). Radiation doses in the DBT+DM arm were 2.3 times higher than those in the control arm.
What this changes or adds
This study adds to a growing body of literature supporting increased cancer detection rates and similar or better recall rates with DBT+DM, compared with conventional mammogram, and suggests that the gain in detection is perhaps even more than previously thought. The findings suggestive of early cancer diagnosis are promising, but whether this early diagnosis will have an impact on prognosis and mortality remains to be seen. In addition, the degree to which DBT is contributing to overdiagnosis remains unclear. Data from forthcoming rounds of screening in this trial are expected to shed light on these important remaining questions, and contribute to a better understanding of the balance between benefits and harms for this screening modality.
Overuse of imaging to evaluate breast pain
Kushwaha AC, Shin K, Kalambo M, et al. Overutilization of health care resources for breast pain. AJR Am J Roentgenol 2018;211:217–223.
What we know
Breast pain is common, is experienced by women across a wide spectrum of ages, can have a negative impact on quality of life, and is often self-limited. Previous studies have documented a low incidence (0%–2%) of breast cancer associated with breast pain. Despite this, existing clinical algorithms include recommendations for breast imaging after completion of the history and physical examination, even when suspicious findings are absent, and specifically when breast pain is localized (as opposed to diffuse). The value (and cost) of imaging in these circumstances is unclear. The goal of this study was to analyze the incidence of breast cancer in women presenting for breast imaging for evaluation of breast pain and to assess the associated costs.
Study results
In this retrospective review of billing databases at three community breast imaging centers in the United States, the authors reviewed demographic characteristics, imaging findings, and associated costs for 799 women (5.7% of all women undergoing diagnostic breast imaging) who presented for evaluation of breast pain. Median age of women presenting with breast pain was 44 years, and pain was focal in 30%, diffuse in 30%, and not localized in the rest. Four hundred fifty-one women (56%) were premenopausal and 292 women (37%) were postmenopausal, while menopausal status for 56 women was unknown. Ninety-four percent were evaluated with mammography, 69% with ultrasound, and 1% with breast magnetic resonance imaging (MRI). While ultrasound detected a benign finding in the area of pain in 5% of women, no cancers or high-risk lesions were detected in the area of pain for any patient with any imaging modality (one cancer was detected in the contralateral asymptomatic breast). The 454 studies performed in women younger than 40 cost an estimated $87,322, while the 745 studies in women older than 40 cost $152,732.
What this changes or adds
This study is the first to report the incidence of imaging evaluations for breast pain in a U.S. community setting (5.7%), and adds to existing reports documenting a lack of association between breast pain (including localized breast pain) as a sole presenting symptom and underlying cancer. In addition, this study highlights the significant costs associated with imaging for this common complaint. These findings suggest that when, after a thorough clinical evaluation (including careful history and physical examination), breast pain is an isolated finding in a woman with up-to-date screening, providers should consider reassurance, supportive measures, and/or follow-up clinical evaluation as initial management strategies of choice. Certainly if breast pain persists, imaging is warranted.
Benefits and harms of screening breast MRI
Buist DSM, Abraham L, Lee CI, et al. Breast biopsy intensity and findings following breast cancer screening in women with and without a personal history of breast cancer. JAMA Intern Med 2018;178:458–468.
What we know
Current guidelines recommend use of annual screening breast MRI in addition to mammogram for women at high risk for breast cancer (>20% lifetime risk). Routine use of this imaging modality is not recommended as part of surveillance for women who have been treated for breast cancer (unless they meet high-risk criteria), or for screening in women considered to be at average or intermediate risk for breast cancer. Despite this, increased use of screening breast MRI has been noted in practice, including for breast cancer survivors. The balance between benefits and harms of breast MRI in these populations remains unclear based on available data. The goal of this study was to assess biopsy intensity and findings in the 90 days following imaging with mammogram or with MRI+mammogram in women with and without a PHBC.
Study results
In this observational cohort study of more than 800,000 women (with and without PHBC) from six Breast Cancer Surveillance Consortium registries undergoing screening from 2003 to 2013, investigators evaluated biopsy intensity and biopsy findings within 90 days of imaging for more than 2 million mammogram and/or breast MRI examinations. In age-adjusted analyses, core and surgical biopsy rates were 2 × and 5 × higher in the 90 days following MRI compared with mammography for women with and without PHBC, respectively. In addition, lower yields of DCIS and invasive cancer were noted following MRI compared with mammography in women with PHBC (with an observed trend toward the same finding in women without PHBC). Finally, more high-risk benign breast lesions were identified following MRI in both groups (with and without PHBC).
What this changes or adds
In demonstrating that women who undergo screening MRI are exposed to higher biopsy rates and lower cancer yield regardless of PHBC, this study supports current guidelines that recommend against routine use of MRI for screening or surveillance in these populations. Providers who recommend breast MRI to women who do not meet specific high-risk criteria should provide education regarding the risk of biopsy with benign results. Further study is required to understand whether specific subgroups of women are more likely to benefit from screening or surveillance breast MRI.
Footnotes
Author Disclosure Statement
No competing financial interests exist.