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Breast cancer risk after atypical ductal hyperplasia may be overstated
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The 10-year risk for invasive breast cancer in women with atypical ductal hyperplasia may be lower than previously reported, according to study results published in JAMA Oncology.
The risk appeared significantly lower in women whose atypical ductal hyperplasia was diagnosed by needle core biopsy rather than excisional biopsy, results showed.
Atypical ductal hyperplasia is a known risk factor for breast cancer, and previous reports estimate the risk for invasive breast cancer after an atypical ductal hyperplasia diagnosis is 29% over 25 years.
“Most of the studies reporting on the increased risk [for] breast cancer in women with atypical ductal hyperplasia were done before the widespread use of screening mammograms and core needle biopsies to evaluate nonpalpable suspicious lesions,” Tehillah S. Menes, MD, surgeon at Tel Aviv–Sourasky Medical Center in Israel, and colleagues wrote. “We speculated that, as imaging technology advances, smaller lesions are observed and biopsied and the risk associated with small foci of atypical ductal hyperplasia detected on core needle biopsy may be lower than risks previously reported from general populations of women with atypical ductal hyperplasia.”
Menes and colleagues evaluated the cumulative invasive breast cancer risk in women diagnosed with atypical ductal hyperplasia by core needle biopsy, compared with women diagnosed by excisional biopsy.
The researchers accessed data from 955,331 women included in the Breast Cancer Surveillance Consortium, an NCI–funded registry of women who undergo mammography in the United States.
Within the entire cohort, 1,727 women were diagnosed with atypical ductal hyperplasia (mean age at diagnosis, 52.6 years; interquartile range, 46.9-60.4). The majority (61.3%; n = 1,058) were diagnosed by core biopsy, and the remaining women (36.8%; n = 635) were diagnosed by excisional biopsy. Researchers observed that the proportion of diagnoses by core needle biopsy increased from 21% in 1996 to 77% in 2012.
Factors associated with the diagnosis included non-Hispanic white race, history of breast cancer in a first-degree relative and high breast density.
Overall, 1,655 invasive breast cancers were diagnosed in the entire cohort during the 10 years of follow-up, 72 of which occurred in women with atypical ductal hyperplasia.
Invasive cancer occurred in 34 women with atypical ductal hyperplasia diagnosis determined on core needle biopsy (3.3%) and 36 women diagnosed on excisional biopsy (6%).
Analyses adjusted for age, race, family history, breast density and mammogram modality showed the cumulative risk for invasive breast cancer was 2.6 (95% CI, 2-3.4) times higher in women with atypical ductal hyperplasia than in those without the diagnosis at baseline.
Diagnosis by excisional biopsy was associated with an adjusted HR of 3 (95% CI, 2-4.5) for invasive breast cancer, whereas core needle biopsy had an adjusted HR of 2.2 (95% CI, 1.5-3.4).
The researchers estimated that 5.7% (95% CI, 4.3-10.1) of women received a diagnosis of invasive cancer in the 10 years following an atypical ductal hyperplasia diagnosis, with a slightly higher risk among women diagnosed via excisional biopsy (6.7% vs. 5%).
Potential study limitations included the lack of a central pathologic review and the inability to assess underascertainment of cancer events.
“Women with atypical ductal hyperplasia diagnosed by core needle and excisional biopsy had a slightly lower risk [for] invasive breast cancer than noted in previously reported studies,” Menes and colleagues wrote. “Because the risk associated with atypical ductal hyperplasia is modified in the presence of other risk factors, clinicians should not recommend increased surveillance and risk-reducing strategies without accounting for other factors. An assessment of an individual’s risk based on multiple factors should be preferred before deciding on prevention strategies.”
Continued surveillance should remain an option for women with atypical ductal hyperplasia, Marissa Howard-McNatt, MD, associate professor of surgical sciences and oncology and director of the Breast Care Center at Wake Forest Baptist Health, wrote in an accompanying editorial.
“I believe that because their risk is still higher than that of the average women, [women with atypical ductal hyperplasia] should be monitored,” Howard-McNatt wrote. “Do we offer them tamoxifen or raloxifene, which are proven therapies to lower the risk [for] future breast cancer? Chemoprevention should be discussed with patients, especially in high-risk groups, such as white women and those with a family history of breast cancer, dense breast tissues, or a history of breast biopsies. We treat our patients best when they are educated about their risks and benefits. This study adds to our and our patients’ knowledge about the contemporary risks for developing invasive breast cancer in patients with atypical ductal hyperplasia.” – by Cameron Kelsall
Disclosures: The researchers and Howard-McNatt report no relevant financial disclosures.
Perspective
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James L. Crawford
This study by Menes and colleagues evaluated 955,331 women — of whom 1,727 were diagnosed with atypical ductal hyperplasia — to determine the incidence of atypical ductal hyperplasia and the associated risk of invasive breast cancer. They hypothesized that the risk for breast cancer associated with atypical ductal hyperplasia diagnosed via core needle biopsy is lower than the reported risks based on historical cohorts. The basis of their hypothesis is that improved imaging technologies, in association with increased use of needle biopsies, results in increased diagnosis of small foci of atypical ductal hyperplasia. Based on the years in which the historical studies were performed, the researchers assumed that the historical cohorts had larger areas of atypia resulting in palpable findings. Therefore, the higher risk for invasive breast cancer in those studies may not be applicable to current findings of small, mammographically found foci of atypical ductal hyperplasia.
The strength of this study is in the use of the NCI–funded Breast Cancer Surveillance Consortium. This is one of the largest repositories of mammograms in existence and allows the use of “big data” to evaluate clinical questions.
It remains unclear whether the estimate of risk posed by atypical ductal hyperplasia in this study is more or less reflective of what occurs compared with the historical cohorts. In this study, tamoxifen was only found to be used by 7% of the women diagnosed with atypical ductal hyperplasia. Because tamoxifen is standard prevention in women with atypical ductal hyperplasia and because it cuts the risk for invasive breast cancer in half, full use of tamoxifen would theoretically reduce the risk after an atypical ductal hyperplasia diagnosis to near normal (with atypical ductal hyperplasia, 5.7% vs. without, 2.2%).
However, it is unclear if the use of tamoxifen was underreported by the patients, making the risk without it higher, or if the risk associated with atypical ductal hyperplasia is less than previously estimated.
Additionally, the true risk posed by atypical ductal hyperplasia may be unclear because of the wide variability in accuracy when pathologists diagnose it on biopsy. According to a study by Joann G. Elmore, MD, MPH, and colleagues, published in JAMA, there is significant disagreement between individual pathologists and expert consensus-derived reference diagnoses when it comes to diagnosing atypia with the overall concordance rate being less than half (48%). Elmore and colleagues’ study demonstrates that there can be a significant increase or decrease in the diagnosis of atypical ductal hyperplasia between pathologists. We do not know the extent of variability in the current study which could skew this study’s results one way or another.
Finally, one could argue that the study underestimates the risk for invasive breast cancer associated with atypical ductal hyperplasia. The researchers do not discuss whether every patient who was diagnosed via core needle biopsy ultimately underwent an excisional biopsy to definitively conclude the absence or presence of invasive breast cancer at the time of diagnosis. Invasive breast cancer can be seen at that site approximately 15% of the time. Such excision and treatment may affect later diagnoses of cancer, resulting in this study’s lower-than-predicted rate at 5.7%.
The researchers raise a valid point in supposing that the current risk for invasive breast cancer in the setting of atypical ductal hyperplasia may be different from historical studies. I applaud their efforts to further characterize the risk for atypical ductal hyperplasia using “big data” to obtain a more accurate risk estimation.
Reference:
Elmore JG, et al. JAMA. 2015;doi:10.1001/jama.2015.1405.
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