Although the principles of managing invasive breast cancer in adolescent girls and young women are the same as in older women, there are a number of management and therapeutic issues requiring special consideration. Adolescents and young women are at particular risk of emotional and psychosocial problems, and require appropriate support from age- and disease-specific psychosocial and medical multidisciplinary teams.39
For many reasons, including development, function, body image, and quality of life, breast-conserving surgery, whenever possible, is obviously desirable for most young women. However, the two principle considerations when deciding between breast-conserving surgery and mastectomy are the risk of local recurrence, as well as the overall cosmetic result. One of the most important risk factors for local recurrence after breast-conserving surgery is age <35 years at presentation,40
as these patients were found to have a nine times higher risk of local recurrence after conservative surgery than patients over 60 years of age.41
However, no studies have demonstrated conservative surgery in young women to have a negative impact on survival.
All young women should be considered at high risk due to age alone, so adjuvant therapies should be considered during management discussions.42
However, the use of adjuvant therapies in young women raises issues of long term side effects, including the induction of an early menopause, fertility impairment, and adverse effects on bone mineral density with chemotherapy and endocrine therapies, and of the development of a second malignancy with radiotherapy.
In addition to the appropriate use of radiotherapy, the current choices of adjuvant therapies for premenopausal patients include cytotoxic chemotherapy, ovarian ablation (by surgery, irradiation, or chemical ovarian suppression), anti-estrogen therapy, or any combination of these modalities. However, the optimal combination of chemotherapy for young women has become more controversial with the advent of recent studies examining the role of taxanes and dose-intensive adjuvant therapies.43
Certainly it is clear that women under 30 years of age with early-stage disease, who do not receive adjuvant chemotherapy, have particularly poor relapse-free survival rates.44,45
At the current time, anthracycline-containing combinations remain the standard of care. Such regimens have been shown to be more effective than a standard cyclophosphamide, methotrexate, 5-fluorouracil (CMF) combination at 5 years of follow-up. For example, cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) compared with CMF showed 5 year relapse-free and overall survival rates of 63% versus 53% (P
= .009) and 77% versus 70% (P
= .03), respectively.46
It is known that adjuvant chemotherapy for early breast cancer in patients under 50 years of age reduces the relative risk of recurrence by 35% and of death by 27%, and adjuvant chemotherapy alone has been shown to be appropriate for patients with ER-negative tumors.47
However, 5 years of adjuvant tamoxifen has been shown to reduce the relative risk of recurrence by 54% in women with ER-positive disease48
and, in the absence of contraindications, all patients with ER-positive tumors diagnosed prior to age 40 require either chemotherapy and endocrine therapy or endocrine therapy alone.
Other clinical trials have shown that patients with node-positive early breast cancer given four cycles of doxorubicin and cyclophosphamide (AC) followed by four cycles of paclitaxel demonstrated a 17% reduction in the risk of recurrence and an 18% reduction in the risk of death compared with four cycles of AC alone,49,50
while the addition of docetaxel resulted in a significant improvement in disease-free and overall survival for patients with one to three positive lymph nodes.51
There is also a clear survival advantage for a dose-intense regimen of AC followed by paclitaxel given every 2 weeks with growth factor support as, with a median follow-up of 36 months, there is a 26% reduction in the risk of relapse (P
= .010) and a 31% reduction in the risk of death (P
= .013) associated with the dose-intensive arms.52
Prior to the advent of targeted therapy for Her2-positive tumors with trastuzamab (Herceptin, Genentech, San Francisco, CA), the ER−/PR-/HER2+ phenotype was associated with the highest risk of breast cancer death. In the trastuzamab era, “triple-negative” tumors now have the worst prognosis and, as mentioned earlier, young women have the highest proportion of these tumors. The development of novel therapies for triple-negative tumors is a much needed and fertile area for research.
Further compounding appropriate therapeutic management decisions is the evidence that premenopausal women who achieve chemotherapy-induced amenorrhea demonstrate a better prognosis than those retaining their menstrual cycle. It follows that amenorrhea may be important in the action of chemotherapeutic agents. Both relapse-free and overall survival are improved significantly by the induction of amenorrhea, although the optimal duration of amenorrhea remains unknown.53-56
However, the likelihood of becoming amenorrheic following adjuvant chemotherapy is inversely dependent on age. Therefore younger women are less likely to gain maximum benefit from the endocrine effect of adjuvant chemotherapy.57
Unfortunately, in trials evaluating ovarian suppression and amenorrhea to date, chemotherapies used now would be viewed as suboptimal and the proportion of very young women (<35 years) in the trials was small.55,58-60
It is difficult, therefore, to draw clear conclusions regarding the potential benefit of chemotherapy-induced amenorrhea or ovarian suppression. Conversely, suppression of ovarian function certainly has the potential to create significant health and quality-of-life problems for very young women, including menopausal symptoms, psychological distress, and the need to adjust personal and family plans. Further trials are required to better evaluate the potential benefit of the addition of optimal endocrine therapy to adjuvant chemotherapy in very young women.