A young woman with a breast mass: What every internist should know
Mastectomy vs lumpectomy
Early-stage breast cancer is managed with definitive surgery. The two options are mastectomy and breast conservation therapy, the latter involving lumpectomy followed by breast radiation therapy.
Multiple randomized studies comparing mastectomy and lumpectomy showed no difference in survival rates, but patients in the lumpectomy groups had higher rates of local recurrence.32 Breast radiation therapy after lumpectomy lowered the rates of local recurrence and breast cancer death.33 Therefore, most patients can opt to undergo either lumpectomy with radiation or mastectomy, depending on personal preference.
However, mastectomy rather than breast conservation therapy is still recommended in cases of prior radiation therapy, inability to achieve negative surgical margins (as in cases of large tumors), multicentric disease (cancer in separate breast quadrants), or multiple areas of calcifications. Mastectomy is also preferred in most pregnant women unless the diagnosis of breast cancer is made in the third trimester and radiation therapy can be given after delivery. Patients who have large lesions in a small breast may also choose mastectomy with breast reconstruction rather than breast conservation therapy. Patients with a history of scleroderma are encouraged to undergo mastectomy because of increased toxicity from radiation treatment.
Sentinel vs axillary lymph node dissection
Knowledge of axillary lymph node involvement is important because it determines the stage in the tumor-node-metastasis (TNM) system, and it influences the choice of further therapy. Therefore, all patients with nonmetastatic invasive breast cancer must have their axillary lymph nodes sampled.
Conventionally, this involves axillary lymph node dissection. Unfortunately, upper extremity lymphedema develops in 6% to 30% of patients within the first 3 years, and in 49% of patients after 20 years following axillary lymph node dissection.34
Sentinel lymph node dissection was developed to minimize this complication. This procedure involves the injection of a blue dye, isosulfan blue (Lymphazurin), around the edge of the tumor or in the dermis overlying the tumor. The most proximal axillary lymph nodes that stain blue are dissected. Alternatively, a radioactive colloid (most commonly technetium sulfur colloid agents) may be injected, allowing sentinel lymph nodes to be identified by lymphoscintigraphy. If no metastases are found in the sentinel lymph nodes, axillary lymph node dissection is not performed.
A prospective study in 536 women found that at 5 years of follow-up, lymphedema developed in only 5% of patients after sentinel lymph node dissection compared with 16% of those who underwent axillary lymph node dissection (P < .001), with comparable outcomes in terms of disease recurrence.35
Case continues: Patient undergoes surgery
The patient elects to undergo lumpectomy with sentinel lymph node dissection. Pathologic review of the resection specimen reveals a 2.5-cm poorly differentiated invasive ductal carcinoma. Sentinel lymph node dissection shows metastases, and therefore axillary lymph node dissection is performed. One of eight lymph nodes removed is positive for metastases. All surgical margins are negative.
POSTOPERATIVE CARE
5. What would be the next step for our patient?
- Radiation followed by observation
- Tamoxifen (Nolvadex) for 5 years
- Observation only
- Chemotherapy followed by radiation therapy and 5 years of tamoxifen
She should receive chemotherapy, followed by radiation therapy and then tamoxifen for 5 years.
Chemotherapy. Almost all patients who have lymph-node-positive disease are advised to undergo chemotherapy.
The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) performed a metaanalysis of 194 randomized trials that compared adjuvant chemotherapy and no treatment in early-stage breast cancer. Chemotherapy led to a 10% absolute improvement in survival at 15 years for women younger than 50 years and 3% in women age 51 to 69.36
Indications for chemotherapy include axillary lymph node involvement, locally advanced disease, and other risk factors for recurrence such as young age at diagnosis, strong positive family history of breast cancer, prior history of breast cancer, or lymph-node-negative, estrogen-receptor-negative tumors that are larger than 1 cm in diameter.
The Oncotype DX assay is a new tool to help oncologists decide whether to use chemotherapy in cases of estrogen-receptor-positive breast cancer, in which the benefit of chemotherapy is uncertain. It is a polymerase chain reaction assay that measures the expression of 16 cancer-specific genes and five reference genes within the breast tumor. Based on the pattern of expression of these genes, breast cancer can be characterized as low-risk, intermediate-risk, or high-risk. Patients in the high-risk group have a high chance of cancer recurrence and benefit from chemotherapy. Patients in the low-risk group are unlikely to have a recurrence or to benefit from chemotherapy.37 It is far less clear if patients in the intermediate-risk group benefit from chemotherapy, but this assay might eventually prove useful in deciding for or against chemotherapy in this group of patients as well.38 The Oncotype DX assay is presently being studied in a clinical trial.
Radiation therapy after mastectomy is recommended in patients who have breast tumors larger than 5 cm or metastases to more than three axillary lymph nodes.39
Antiestrogen therapy. After chemotherapy, patients with estrogen-receptor-positive cancers also receive 5 years of antiestrogen therapy. Available antiestrogen agents for such patients include tamoxifen, which is a selective estrogen receptor modulator, and drugs called aromatase inhibitors that block conversion of androgens to estrogens in peripheral tissues. Anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are examples of available aromatase inhibitors. Premenopausal women are treated with tamoxifen, and postmenopausal women are offered aromatase inhibitors.
Table 4 lists the most common adverse effects of these agents. Aromatase inhibitors are associated with a higher risk of osteoporosis and arthralgia, while tamoxifen increases the risks of thromboembolism, endometrial cancer, and vaginal discharge. Both agents may produce menopausal symptoms such as hot flashes and mood swings.
