According to Harrison's, “There is no justification for adjuvant chemotherapy in women with tumors <1 cm in size whose axillary lymph nodes are negative” for metastatic signs. These “Stage 0” carcinomas receive no pharmaceutical treatment. More advanced cases are treated as summarized in Table 1 and further expounded below.
| Age group | Lymph node status | Endocrine receptor status | Tumor | Recommendation |
|---|---|---|---|---|
| Premenopausal | Negative | Negative | >2 cm, or 1-2 cm and other poor prognostic variables | Multidrug chemotherapy |
| Premenopausal | Negative | Positive | >2 cm, or 1-2 cm and other poor prognostic variables | Multidrug chemotherapy + Tamoxifen |
| Premenopausal | Positive | Negative | Any | Multidrug chemotherapy |
| Premenopausal | Positive | Positive | Any | Multidrug chemotherapy + Tamoxifen |
| Postmenopausal | Negative | Negative | >2 cm, or 1-2 cm and other poor prognostic variables | Consider multidrug chemotherapy |
| Postmenopausal | Negative | Positive | >2 cm, or 1-2 cm and other poor prognostic variables | Tamoxifen |
| Postmenopausal | Positive | Negative | Any | Multidrug chemotherapy |
| Postmenopausal | Positive | Positive | Any | Tamoxifen, with or without chemotherapy |
Tamoxifen is an “antiestrogen” agent, a form of hormone therapy, not technically chemotherapy. Where indicated above, it should usually be administered following completion of chemotherapy, not concurrently. It is typically administered only in those cases with positive ER.
Some survival advantage to chemotherapy has been shown in postmenopausal women, but the benefits are controversial. Tamoxifen in these women improves survival for patients with or without positive lymph node status, but survival improvement is modest in cases where multiple lymph nodes are involved. For this reason, chemotherapy is often used for patients without contraindications who have more than one involved lymph node, and tamoxifen is there given simultaneously or subsequently. Tamoxifen may be used without chemotherapy in postmenopausal women with a more positive prognosis.
“Neoadjuvant therapy” is more recently being used. This is adjuvant therapy prior to surgery and radiation; in up to 75% of patients, this allows “downstaging”, often allowing breast conservation. At least one randomized study failed to find any difference in survival.
Nearly half the patients treated for breast cancer develop some form of metatstatic disease. The choice of therapy requires consideration of local therapy needs, the overall medical condition of the patient, and the hormone receptor status of the tumor, as well as the exercise of clinical judgment. Because therapy of systemic disease is palliative, the potential toxicities of therapies should be balanced against the response rates. Several variables influence the response to systemic therapy. For example, the presence of estrogen and progesterone receptors is a strong indication for endocrine therapy, since the response rates for tumors that express both receptors may approach 70%. On the other hand, patients with short disease-free intervals, rapidly progressive visceral disease, lymphangitic pulmonary disease, or intracranial disease are unlikely to respond to endocrine therapy.
Unlike many other epithelial malignancies, breast cancer responds to several chemotherapeutic agents, including anthracyclines, alkylating agents, taxanes, and antimetabolites. Multiple combinations of these agents have been found to improve response rates somewhat, but they have had little impact on duration of response or survival. As previously mentioned, median survival from diagnosis of metastatic disease is approximately 2 years. The choice among multidrug combinations frequently depends on whether adjuvant chemotherapy was administered and, if so, what type. While patients treated with adjuvant regimens such as cyclophosphamide, methotrexate, and fluorouracil (CMF regimens) may subsequently respond to the same combination in the metastatic disease setting, most oncologists use drugs to which the patients have not been previously exposed. Once patients have progressed after combination drug therapy, it is most common to treat them with single agents. Given the significant toxicity of most drugs, the use of a single effective agent will minimize toxicity by sparing the patient exposure to drugs that would be of little value. Unfortunately, no form of in vitro drug sensitivity testing to select the drugs most efficacious for a given patient has been demonstrated to be useful.
Most oncologists use either an anthracycline or paclitaxel following failure with the initial regimen. However, the choice has to be balanced with individual needs.
“Locally advanced” (Stage III) breast cancer is often difficult to remove surgically, especially if there is chest wall involvement. Although no randomized trials have proved the efficacy of induction chemotherapy, this approach has gained widespread use. More than 90% of patients with locally advanced breast cancer show a partial or better response to multidrug chemotherapy regimens that include an anthracycline. Early administration of this treatment reduces the bulk of the disease and frequently makes the patient a suitable candidate for salvage surgery and/or radiation therapy.