The increased use of breast cancer screening has led to increased detection of smaller cancers. Many of the original adjuvant studies did not include patients with tumors under 1.0 cm. The use of central venous access devices and the improvement in antiemetics have made it easier to give chemotherapy. New chemotherapy and endocrine and targeted therapies are increasingly available. The challenge becomes determining who needs which treatment, how much and for how long.

Treatment planning depends on the tumor type and grade, the size of the cancer, and the extent of metastatic tumor (if any) in lymph nodes. For some patients, newer genomic-based studies may contribute information that impacts decision making, particularly the use of chemotherapy. Estrogen receptor status remains a key factor for decision making. All patients with positive estrogen receptors should be considered for endocrine therapy as a component of their systemic therapy. Generally, estrogen receptor-positive patients have a better prognosis. The higher levels of estrogen receptor expression (over 10%) probably respond better to endocrine therapy, but patients with any level of estrogen receptor staining should be considered for a trial of endocrine therapy. Estrogen receptor-negative cancers should be considered for chemotherapy.

Progesterone receptor levels are also routinely measured. A patient with an estrogen-negative/progesterone-positive tumor should be considered for endocrine therapy though these patients have a poorer prognosis than patients with estrogen- and progesterone-positive tumor [19].

HER2 expression was once considered a poor prognostic feature. However, the remarkable efficacy of trastuzumab added to systemic therapy has resulted in significant improvement in prognosis [19]. Newer studies support the addition of pertuzumab to trastuzumab for neoadjuvant and metastatic therapy regimens.

Ki-67 provides information on the proliferation status of the cancer, but the utility of the assay remains limited due to challenges in standardization of the assay. In general, lower scores, less than 15%, suggest that the patient has a less aggressive cancer. Higher scores suggest faster growth and potentially more aggressive cancers. Ongoing clinical trials are evaluating the change in Ki-67 levels during neoadjuvant endocrine treatment and attempting to standardize the assay. Sustained reduction in the Ki-67 to <10% appears to predict excellent outcomes with endocrine therapy alone.

Several genomic-based tests are available to help in decision making for stage 1 and 2 breast cancers. All breast cancer patients may derive benefit from chemotherapy to reduce the chance of recurrence. Genomic-based assays have been developed to identify those patients most likely to benefit from chemotherapy. They are most useful for the estrogen receptor-positive cancers, particularly those with minimal or no nodal involvement. They are generally not useful for patients with HER2 overexpression. Oncotype DX, MammaPrint, and Prosigna (formerly called PAM50) are three of the better known gene expression assays that provide prognostic information [13, 18, 22]. Though the three tests provide slightly different information, they all stratify patients into higher risk versus lower risk for recurrence. Oncotype DX stratifies patients into low risk, moderate risk, and high risk of recurrence [18]. Patients at low risk for recurrence should only be treated with endocrine therapy since chemotherapy does not provide significant improvement to their excellent prognosis with endocrine therapy alone. High-risk patients should be offered chemotherapy followed by endocrine therapy to give them the best opportunity for long-term survival without recurrence. The results from the TAILORx clinical trial evaluating the best treatment for moderate-risk patients should be reported in the near future. Mammaprint provides a high risk/low risk stratification.

The tumor size and the extent of lymph node involvement remain important in the treatment decision making process. Neoadjuvant endocrine and systemic therapies had previously been reserved for locally advanced and inflammatory breast cancer [11]. Based on data from several clinical trials, neoadjuvant chemotherapy can now be considered for any patient with a tumor larger than 2 cm or with biopsy-documented lymph node involvement [14]. Neoadjuvant therapy may allow the patient to have lesser surgery and have fewer nodes removed. It also demonstrates the responsiveness of the cancer to treatment. Pathologic response to treatment may be useful in determining need for additional therapy and the risk of recurrence.

Education and collaboration are keys to identifying optimal therapy for a breast cancer patient. Once a diagnosis has been established with characterization of the phenotype and the proper imaging has been completed, the medical oncologist and the patient are ready to begin the interactive process that will determine the systemic treatment plan. Sometimes this will begin after a patient has surgery and the pathologic stage is known. A critical aspect of these discussions is helping patients understand their risk of disease recurrence balanced against the potential side effects of the therapies. Patients with comorbid conditions including complications of advanced age, renal failure, or liver failure may not be able to tolerate some therapies. A clear discussion of side effects and providing the patient with information that can be reviewed again at home help with patient and caregiver understanding. Online models such as Adjuvant! Online can be useful to visually demonstrate the risks of recurrence and the benefits of treatment. However, a challenge to use of these tools is the need for updating as new information becomes available. Adjuvant! Online also does not incorporate data on HER2 status in its current model.

Professional societies and organizations have increasingly provided guidelines for treatment. One of the more important organizations is the NCCN which has established programs for developing and updating treatment algorithms for most cancers. Information is available both for clinicians and patients [16]. The breast cancer algorithms are comprehensive and are frequently updated. ASCO guidelines are not as comprehensive but also include many guides for supportive care such as antiemetic use and growth factor use.

Women of childbearing potential who wish to optimize the possibility of pregnancy following systemic cancer therapies need referral to a fertility specialist for discussion about treatment options. Chemotherapy may cause early menopause with permanent ovarian failure. Long-term endocrine therapy may impact decision making about pregnancy following the treatment for cancers.

During treatment it is important to emphasize global patient health and wellness particularly for those women who have an excellent prognosis. Patients should be encouraged to exercise and stay active. Although tobacco is not directly linked to breast cancer, counseling for tobacco cessation should be offered as part of good global health practice. It is often difficult to lose weight during treatment for breast cancer. Women should be encouraged to seek a healthy weight as part of their long-term survival plan. Comprehensive care requires programs to provide support for patients during and after cancer treatment. Nutrition classes should be available on a regular basis with individual counseling if possible. Lymphedema management should be available to all patients who have had nodal surgery or irradiation. Counseling and guidance for navigating the financial challenges of cancer management are essential. A process for directing patients to legal support is important particularly for help with medical directives, wills, guardianship, and job discrimination during and after the treatment. Medical patient education is a very important piece of comprehensive patient care. An educated patient and caregiver team will be better equipped to face the rigors of treatment with greater confidence and assurance.

Endocrine therapy is the oldest systemic therapy for breast cancer. The original treatments with bilateral oophorectomies and adrenalectomies have been replaced by medications that interfere with the estrogen receptor function or block postmenopausal estrogen production. Tamoxifen, a selective estrogen receptor modulator, is approved for use at any age and at any stage and can be used for both male and female breast cancers. The side effects include hot flashes, a risk of deep vein thrombosis, and a rare risk of uterine cancer. The third-generation aromatase inhibitors (anastrozole, letrozole, exemestane) are also approved for any stage of estrogen-positive breast cancer [5, 6]. These medications are only effective if the ovaries are nonfunctioning either in natural menopause or in women with premature ovarian failure due to chemotherapy or oophorectomies. There is a slight benefit to using aromatase inhibitors rather than tamoxifen in postmenopausal women. Side effects can include diffuse arthralgia, hair thinning, and bone loss. Compliance can be an issue if the side effects of hormonal therapy are intolerable. Clinicians need to monitor compliance and work with patients to find suitable interventions or change the medication to support compliance with treatment.