Personal History
The majority of all breast biopsies are benign. In general, the findings are important only because they provide reassurance for the patient and the physician. The finding of either atypical hyperplasia or lobular carcinoma in situ (LCIS) at biopsy has significant implications, however; women whose biopsies demonstrate either pathologic entity are at increased risk for future development of breast cancer. These two findings are present in approximately 1-5% of breast biopsies, depending on the completeness of the pathologic examination.

Atypical hyperplasia refers to proliferative breast disease in which the appearance of the ductal or lobular epithelium is significantly altered from that of the normal breast epithelium. Several large, retrospective studies have served to define the relative risk of breast cancer in the population of women who have this pathologic finding.

Compared to the general population, the presence of atypical hyperplasia in a woman with no family history of breast cancer indicates a relative risk of breast cancer development of approximately 3-4. If there is a family history of breast cancer in a first-degree relative, the relative risk increases to over 8. Perhaps more helpful in counseling women is the absolute risk of breast cancer development over a 20 year period. If atypical hyperplasia is present, a woman has an approximately 15-20% likelihood of developing breast cancer in either breast over that period of time.

Lobular carcinoma in situ in a biopsy specimen also indicates an increased risk of future breast cancer development. Pathologically, this refers to a finding of cytologically malignant cells distending the lobular units. Despite the malignant appearance of these cells, LCIS does not act in a malignant fashion, neither invading nor metastasizing. While LCIS itself is entirely benign, follow-up studies of patients with this finding demonstrate a risk of between 15-30% for future breast cancer development. As with atypical hyperplasia, the breast in which the LCIS is discovered is not necessarily the breast in which a cancer will develop. One-half of all breast cancers will be identified in the contralateral breast.

A woman’s future risk of breast cancer may be altered not only by the findings of a benign breast biopsy but also by a personal history of breast cancer. Once a patient has been treated for a breast cancer, her risk for future breast cancer is significantly increased over that of the general population.

Due to the increased use of lumpectomy and radiation therapy for the treatment of early breast cancers, many women continue to be at risk for the development of disease in the same breast in which their initial breast cancer was diagnosed. By 10 years, this risk could be 10% or higher. Additionally, all women who are treated for breast cancer, whether with mastectomy or with breast-conservation therapy, are at risk for the development of a contralateral cancer.

Various studies have shown this risk to be between 0.5-1% per year. Thus, by 20 years postdiagnosis of her initial breast cancer, a woman has up to a 20% risk of disease in the opposite breast. Table 4.4 summarizes the risks associated with a woman’s biopsy history.

Reproductive Factors
Epidemiologic data clearly demonstrate that reproductive factors influence a woman’s risk of breast cancer. There is a slight but consistently evident increase in the incidence of breast cancer in women who have early menses and late menopause. Additionally, an early age at first full-term pregnancy appears to be somewhat protective of breast cancer risk.

The mechanism by which these factors influence breast cancer risk appears to be the cyclical hormonal stimulation of the breast. Continuous, uninterrupted stimulation of the breast tissue on a monthly basis promotes proliferation of breast cells. The greater the number of cycles the breast experiences, the more likely there is to be uncontrolled proliferation of cells and eventual breast cancer cell growth. Any decrease in the absolute number of cycles should theoretically decrease the risk of breast cancer. Likewise, an interruption of the normal cycling should also be protective.

Data regarding natural menopause indicate that women who undergo menopause after the age of 55 have twice the risk of breast cancer of women undergoing menopause before the age of 45. Early oophorectomy (before the age of 50) also appears to have a protective effect on breast cancer risk.

Additional studies indicate that a full-term pregnancy by the age of 30 may reduce risk by up to 30 % and that a full-term pregnancy by the age of 20 reduces risk by 50%.

Table 4.4. Relative risks associated with pathologic biopsy findings While data regarding endogenous hormonal factors are fairly consistent, the data regarding the role of exogenous estrogens in the promotion of breast cancer risk are somewhat less well established. Studies of oral contraceptives and of hormone replacement therapy (HRT) have yielded conflicting results. It is likely, however, that long-term use of either agent does increase the risk of breast cancer slightly.

Recent studies of HRT and breast cancer risk indicate that women who are currently using HRT are at increased risk for breast cancer development. A meta-analysis of the largest studies, however, suggests that the increased risk is only about 10% and is of questionable statistical significance.

Those women who have taken HRT in the past but are not currently using it are not at increased risk. Interestingly, multiple studies have now shown that the risk of death from breast cancer is lower in women diagnosed while taking hormonal therapy. It is unclear what biologic event is responsible for this finding.

In the past, almost every study investigating oral contraceptive use and breast cancer risk concluded that there was a significant increase in risk associated with their use. The majority of recent studies regarding oral contraceptive use and breast cancer risk, however, have shown that their use has little impact upon breast cancer incidence rates. Even in women who have used oral contraceptives for extended periods of time (greater than 10 years), there is only a minimal, nonsignificant increase in breast cancer cases.

This increase is seen most commonly in the group of women who begin using oral contraceptives at a young age (<20 years). Mortality from breast cancer is not affected by the use of oral contraceptives, either at the time of diagnosis or prior to diagnosis. Furthermore, in studies evaluating risk of breast cancer and either oral contraceptive or HRT use, the presence of a family history of breast cancer does not appear to increase the risk of breast cancer further.