As previously discussed, in unscreened populations (including young women, for whom screening is not indicated) most breast cancers are detected as a palpable mass by the affected patient. Such carcinomas are almost all invasive and are typically at least 2 to 3 cm in size. At least half of these cancers will already have spread to regional lymph nodes. In older screened populations, approximately 60% of breast cancers are discovered before molecular inhibitors of HER2, outcomes were similar to symptoms are present. About 20% are in situ carcinomas. patients with triple-negative carcinomas. However, com-Invasive carcinomas detected by screening in older women plete response rates exceed 60% when targeted therapy is are 1 to 2 cm in size and only 15% will have metastasized combined with chemotherapy, and the outlook for these to lymph nodes. Palpable cancers in the older age group patients has been markedly improved. are often “interval” cancers—cancers that appear suddenly • RNA expression profiling is a newer method of subclasbetween screening intervals. Understandably, interval sifying cancers. For breast cancers, many of the genes cancers generally are highly proliferative and usually are that predict prognosis are involved in proliferation. high grade. The greatest clinical value of these assays is their http://ebooksmedicine.net
The clinical outcome for a woman with breast cancer ability to identify patients with slow-growing, anti-can be predicted based on the molecular and morphologic estrogen-responsive cancers who can be spared the features of the cancer and its stage at the time of diagnosis. toxicity of chemotherapy. Factors that influence outcome include the following: • Tumor stage. “Stage” is a measure of the extent of tumor • Biologic type. The biologic type of cancer is evaluated by at the time of diagnosis and is important for all biologic a combination of histologic appearance, grade (includ-types of carcinoma. It is based on features of the primary ing proliferative rate), expression of hormone receptors, tumor (T), involvement of regional lymph nodes (N), and expression of HER2. and the presence of distant metastases (M) (
Fig. 19.30
Proliferation is evaluated by mitotic count and is The AJCC/UICC staging system, used in the United closely tied to responsiveness to cytotoxic chemother-States and Europe, classifies tumors as T1, T2, and T3 apy. This is because rapidly growing cancer cells are based on the tumor size, whereas T4 tumors have ulcer-more sensitive to agents that damage DNA or otherwise ation of the skin, involvement of the deep muscles of interfere with cell division. the chest wall, or are clinically diagnosed as inflamma-
Expression of estrogen or progesterone receptors pre-tory carcinoma. The majority of cancers first metastasize to dicts response to anti-estrogen therapy. The growth of regional nodes, and nodal involvement is a very strong hormone receptor–positive cancers can be inhibited for prognostic factor. Lymphatic drainage goes to one or many years with therapy and it is possible for patients two sentinel lymph nodes in the axilla in most patients. to survive for long periods with distant metastases. If these nodes are not involved, the remaining axillary However, resistance often eventually develops—in nodes are usually free of carcinoma. Sentinel node biopsy some cancers because of mutations in the gene for ER. has become the standard for assessing nodal involve-In contrast, there is no targeted therapy available for ment, replacing more extensive lymph node dissections, triple-negative cancers, which are treated with chemo-which are associated with significant morbidity. Distant therapy. Cancers that do not respond to initial therapy metastases (M) are only detected in 5% of newly diagmetastasize and usually cause the death of the patient. nosed women. Stage 0 is CIS, which is associated with