Testing for tumor markers such as estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2) expression status in biopsy-proven breast cancer is now the standard of care. Seventy percent of breast cancers are estrogen receptor-positive, with increasing frequency associated with older age.34 Estrogen/progesterone receptor positivity is associated with a more favorable outcome, and multiple hormonal therapies can be aimed at these receptors.34 While HER2 overexpression—which occurs in 15% to 30% of newly diagnosed breast cancers35—is associated with more aggressive tumors, women with this type of tumor cell can benefit from trastuzumab, an anti-HER2 drug.36
Key factors that affect prognosis
Important factors affecting prognosis and treatment of localized breast cancer are tumor size, age and menopausal status, tumor expression of hormone receptors and/ or the HER2 protein, as well as the status of the draining axillary nodes. Factors that predict a greater chance of recurrence include the spread of disease to axillary nodes, larger tumor size, invasive histology, inflammatory pathology, lack of estrogen/progesterone receptors, and age <50 years or premenopausal status.
Treatment options include surgical resection, radiation, and systemic adjuvant therapy in the form of chemotherapy, endocrine therapy, or anti-HER2 monoclonal antibodies.37 (For more on treatment, see “Surgery, radiation, and systemic therapy: Making the most of what’s in our arsenal” at jfponline.com.)
Don’t overlook quality-of-life issues
Follow-up of breast cancer patients should go beyond treatment and work-up for recurrence and metastatic disease to focus on health and lifestyle issues, such as stress reduction, mood, smoking cessation, diet and exercise, treatment of hot flashes, sexual dysfunction, and bone health. A recent study found both reduced recurrence and increased survival in women receiving psychological interventions to improve quality-of-life measures after an 11-year follow-up.38
Refer women to targeted Web sites such as the National Breast Cancer Awareness Month organization (http://www.nbcam.org/), the National Breast Cancer Foundation (http://community.nationalbreastcancer.org/), and the Susan G. Komen Breast Cancer Foundation (http://ww5.komen.org/). Offer treatment for bothersome symptoms. Hot flashes and depression, for example, often related to endocrine therapy, can be treated with selective serotonin reuptake inhibitors (SSRIs). That said, some SSRIs decrease the active metabolite of tamoxifen by inhibiting CYP2D6 enzyme and must, therefore, be used with caution. However, venlafaxine and citalopram are less likely to alter tamoxifen metabolism than other SSRIs.39
CASE When Carrie was 47, she had an abnormal MRI of the left breast. Core needle biopsy and pathology of the lesion revealed an estrogen and progesterone receptor-positive tumor that was negative for HER2 overexpression. She underwent lumpectomy, which revealed a 1.5 cm tumor, followed by a negative sentinel node biopsy, and was diagnosed with stage I (T1N0M0) breast cancer. Carrie had radiation after surgery; she did not require chemotherapy, but was told to take tamoxifen for 5 years. This adjuvant endocrine therapy led to hot flashes and depression, both of which were successfully treated with venlafaxine. Carrie is currently cancer-free and participates in a breast cancer survivor program that includes regular visits with her primary physician and her oncologist.
CORRESPONDENCE Denise Sur, MD, 1920 Colorado Avenue, Santa Monica, CA 90404; dsur@mednet.ucla.edu
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Surgery, radiation, and systemic therapy: Making the most of what’s in our arsenal
Breast cancer surgery has changed dramatically over the years. Multiple studies have shown that breast-conserving therapy (lumpectomy followed by radiation) for carefully selected women is comparable to mastectomy for local recurrence and survival. While there has been much interest in determining whether a subset of patients could forego radiation after lumpectomy, a meta-analysis by the Early Breast Cancer Trialists Collaborative Group demonstrated that radiation after lumpectomy provides an absolute local recurrence risk reduction of 19%, and a 5.4% absolute reduction in 15-year breast cancer mortality rates compared with lumpectomy without radiation.1 Thus, radiation after lumpectomy remains the standard of care for all women undergoing breast-conserving therapy, regardless of tumor characteristics.
In certain women with a high risk of recurrence (≥4 positive nodes), radiation is also recommended after mastectomy. Women undergoing mastectomy have numerous options for immediate or delayed breast reconstruction. Consultation with a multidisciplinary team, including a plastic surgeon, prior to any surgical intervention is advised.2
Multiple systemic chemotherapy regimens have been shown to be beneficial in carefully selected patients with breast cancer. Systematic reviews have demonstrated that an anthracycline-based regimen can decrease annual breast cancer mortality by 38% in women <50 years old and by 20% in women ages 50 to 69 years.1 in more recent randomized controlled trials, the addition of taxanes to anthracycline-based regimens has produced promising results.3
Numerous hormonal therapies benefit women with estrogen or progesterone receptor-positive breast cancer. Tamoxifen blocks the activity of estrogen on receptors located in breast cancer tissue, for example; aromatase inhibitors block the conversion of androgens to estrogen; and gonadotropin-releasing hormone (GnRH) analogs such as leuprolide and goserelin suppress ovarian production of estrogen.
For postmenopausal women, options include an aromatase inhibitor alone or tamoxifen followed by an aromatase inhibitor.
In premenopausal women, aromatase inhibitors are not very effective, as decreasing peripheral estrogen stimulates the ovaries to produce more estrogen. Thus, for these patients, adjuvant endocrine therapy consists of tamoxifen, with ovarian ablation (via surgery or radiation) or ovarian suppression with a GnRH analog. If the patient goes through menopause as a result of this therapy, she may benefit from aromatase inhibitors at that time.4,5
Women with breast cancer that overexpresses the HER2 gene benefit from adjuvant treatment with trastuzumab, an anti-HER2 antibody.6 While current guidelines advise treatment for 1 year, multiple studies are evaluating dosing schedules and optimal duration of treatment. for now, patients should be monitored for signs of cardiotoxicity at baseline and every 3 months thereafter until completion of therapy.4
References
1. Early Breast Caner Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;265:1687-1717.
2. Codeiro P. Breast reconstruction after surgery for breast cancer. N Engl J Med. 2008;359:1590-1601.
3. DeLaurentiis M, Cancello G, D’Agostino D, et al. Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol. 2008;26:44-53.
4. National Comprehensive Cancer Network. Breast cancer risk reduction clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2003;1:280-296.
5. Baum M, Budzar AU, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002;359:2131-2139.
6. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Herceptin adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659-1672.