Atypical Hyperplasia of the Breast — Risk Assessment and Management Options

Sept. 14, 2015

Take-Home Message:

“The younger a woman is when she receives a diagnosis of atypical ductal hyperplasia, the more likely it is that breast cancer will develop…” in her lifetime; however, if women with atypical ductal hyperplasia take medication to prevent breast cancer, their risk of developing breast cancer may be reduced by over 40% and up to approximately 80%.

RISK:
  • “The younger a woman is when she receives a diagnosis of atypical ductal hyperplasia, the more likely it is that breast cancer will develop.”
  • “Atypical hyperplasia confers an absolute risk of later breast cancer of 30% at 25 years of follow-up.”
  • “The cumulative incidence of breast cancer appeared to increase linearly overtime.”

PREVENTION:
Clinical "trials have shown pharmacologic risk reduction (taking medication to prevent cancer) to be effective in women with atypical hyperplasia”
Tamoxifen, raloxifene (Evista) and exemestane have been proven to reduce the risk of developing breast cancer in women who have atypical hyperplasia

 

“Education regarding chemoprevention (taking medication to prevent cancer) should describe a woman’s absolute risk of breast cancer, the anticipated reduction in risk, and the absolute risks of various side effects.”
An individual’s personal benefits and risks of taking risk-reduction medication should be discussed with her physician.

SCREENING:
“At present, there are no prospective data that address the value of screening MRI for women with atypical hyperplasia.”
Studies are needed to determine the recommendation of using screening breast MRI in patients with atypical hyperplasia. For now, the use of screening breast MRI is a discussion for individual patients and their physicians.

BOTTOM LINE:
“Breast cancer will not develop in the majority of the women (with atypical hyperplasia).” And “Even among those in whom breast cancer does develop, the diagnosis may occur at an age at which their risk of death from other causes is higher than their risk of death from breast cancer.”
 

Summary:

Atypical Hyperplasia of the Breast — Risk Assessment and Management Options​
Authors: Lynn C. Hartmann MD, Amy C. Degnim MD, Richard J. Santen MD, William D. Dupont PhD, Karthik Ghosh MD
Source: N Engl J Med 2015;372(1):78-89 Atypical Hyperplasia of the Breast — Risk Assessment and ...

Atypical hyperplasia is found in approximately 10% of all benign breast biopsies.  There are two types of atypical hyperplasia based on microscopic appearance, atypical ductal hyperplasia and atypical lobular hyperplasia.  They are considered to be high-risk, premalignant breast lesions.  When these lesions are diagnosed on core needle biopsy, surgical excision is recommended to rule out a nearby underlying breast cancer.  With atypical ductal hyperplasia, the risk of finding cancer at the time of surgical excision is 15%-30%. 

Once a woman is diagnosed with atypical hyperplasia, she has a cumulative incidence of breast cancer (either ductal carcinoma in situ or invasive cancer) of 30% over the next 25 years, based on the Mayo Clinic Cohort study.  The risk of breast cancer is higher in those diagnosed with atypical hyperplasia at a younger age and in those with a greater number of foci containing atypia.  The Breast Cancer Risk Assessment Tool, which is available online and widely used by practitioners to counsel women on their risk, significantly underestimates breast cancer risk in women with atypical hyperplasia.  The authors of this paper therefore recommend using cumulative incidence data instead when atypical hyperplasia is present.

97% of atypical ductal hyperplasia and 88% of atypical lobular hyperplasia has estrogen receptor staining, meaning it is stimulated by estrogen.  Because of this, medications called selective estrogen receptor modulators (for example, tamoxifen and raloxifene) and aromatase inhibitors (for example, exemestane, anastrozole, and letrozole) have been shown in clinical trials to effectively reduce the risk of breast cancer associated with these lesions.  A recent meta-analysis of selective estrogen receptor modulator trials found a 38% relative reduction in the risk of breast cancer in those taking the medication.  Relative risk reductions in the atypical hyperplasia subgroup were even greater and ranged from 41% up to 79%. 

Despite the evidence that chemoprevention medications work, patients are reluctant to take them due to fear of side effects.  Vasomotor symptoms (that is, hot flashes, night sweats) are not uncommon; they occurred in 117 per 1000 high-risk women on tamoxifen in the NSABP P-1 and in 67 per 1000 women on exemestane in the MAP.3 trial.  The serious risks associated with tamoxifen and raloxifene are related to thromboembolic events, including deep venous thromboses and pulmonary emboli, and are infrequent.  The risk of venous thromboembolisms with these medications ranges from 5.9 to 14 per 1000 women.  Tamoxifen (but not raloxifene or the aromatase inhibitors) is also associated with an increased incidence of endometrial cancer of 5.5 per 1000 women, mainly in those who are postmenopausal.