Partly owing to inadequate screening options for young women, breast cancer in young patients tends to be diagnosed at a more advanced stage, with more stage 2 and 3 disease diagnosed than in older women (9, 12). Consequently, young women may more likely need or benefit from preoperative systemic therapy than older women, although available data in this area are limited (37). Despite the large benefit that young women obtain from an irradiation boost to the tumor bed, most studies continue to indicate that young age is a risk factor for local recurrence, for both invasive and noninvasive disease (38, 39 and 40) (Fig. 85-2). No evidence suggests, however, that mastectomy in young women improves survival compared with breast conservation, likely because these women are also at increased risk of systemic recurrence (41, 42). In a population-based Danish cohort of 9,285 premenopausal women with breast cancer, the incidence of local recurrence was 15.4% after breast-conserving therapy among the 719 women under age 35 compared with 3.0% in women ages 45 to 49, although no difference was found in the risk of death between the two age groups (42). Thus, young age alone is not a contraindication to breast conservation. Nonetheless, an increasing number of young women are opting not only for mastectomy, but for contralateral prophylactic mastectomy (43). Reasons for this trend are not completely clear, nor is there evidence that such aggressive surgical measures will improve outcomes. For some young women, local therapy decisions may be influenced by the presence or absence of a known genetic risk for new primary breast cancer (i.e., a BRCA1 or BRCA2 mutation). Thus, prompt genetic counseling and testing for young women at risk for harboring a deleterious genetic mutation should be considered, especially for women for whom the results would have an impact on local therapy decisions. Bilateral prophylactic mastectomy and oophorectomy are increasingly considered for young women with known BRCA1 or BRCA2 mutations, despite the current lack of clear benefits of such risk-reducing strategies in breast cancer survivors (44, 45).

At present, no relevant data are available on the late effects of radiation therapy plus modern systemic therapy (including anthracyclines, taxanes, and trastuzumab) on cardiac functioning in young women. Moreover, other effects of radiation therapy in patients with very long life expectancy must be taken into account (46).

Attention to margin status may be particularly important for young women undergoing breast conservation treatment. In one evaluation including 37 women younger than age 35 with lymph node-negative breast cancer having breast-conserving therapy, local recurrence rates were 50.0% for women with positive margins compared with 20.8% for those with negative margins (47). In a more recent publication, women age 40 or younger with invasive disease had 10-year local recurrence-free survival of 84.4% with negative margins versus 34.6% with positive margins, whereas women over age 40 had local recurrence-free survival of 94.7% if margins were negative compared with 92.6% if margins were positive (48). These findings translated to a 10-year distant disease-free survival (DFS) of 72.0% for younger women with negative margins compared with 39.7% (relative risk [RR] = 3.4) for the younger age group with positive margins, whereas for older women, no significant difference was seen in DFS among those with negative compared to positive margins. There is also evidence that young women may benefit additionally from postmastectomy breast irradiation in the setting of one to three positive axillary lymph nodes (49). Despite the clear benefits, recent population-based data suggest that very young women may be less likely to receive adjuvant breast irradiation after breast-conserving surgery (50). Further research is needed to understand these trends.

Adjuvant treatment recommendations are based on tumor and patient characteristics predicting the risk of systemic recurrence and potential responsiveness to therapy, as well as the patient’s preferences and values. Increasingly, treatments are tailored, regardless of age, to the phenotypic subtype of the tumor as assessed by conventional factors, such as grade, proliferation rate, estrogen and progesterone receptors, and ERBB2 expression. More recent application of genetic signature technology has provided additional predictive information regarding the degree of risk and responsiveness to therapy (see Chapter 31). However, most of the data on adjuvant treatment response was obtained during an era when details related to endocrine responsiveness were either incomplete or imprecise. Even today, endocrine responsiveness evaluation requires improved reporting of steroid hormone receptors and a better understanding of the role of ERBB2 overexpression and amplification (51). Currently it is recommended that the estimation of
endocrine responsiveness should be the first consideration in tailoring adjuvant therapies for patients with breast cancer, regardless of age (52). Adjuvant chemotherapy has historically been used extensively in premenopausal patients because of its overwhelming beneficial effects on outcome (53). The incremental benefits of newer cytotoxic drugs and regimens, including the addition of the taxanes, dose density, and trastuzumab, appear to be present across age groups, although data for very young women are limited (54, 55, 56, 57 and 58).