TREATMENT: Breast Cancer
One of the most exciting aspects of breast cancer biology has been its recent subdivision into at least five subtypes based on gene expression profiling.
Luminal A: The luminal tumors express cytokeratins 8 and 18, have the highest levels of estrogen receptor (ER) expression, tend to be low grade, are most likely to respond to endocrine therapy, and have a favorable prognosis. They tend to be less responsive to chemotherapy.
Luminal B: Tumor cells are also of luminal epithelial origin but with a gene expression pattern distinct from luminal A. Prognosis is somewhat worse that luminal A.
Normal breast–like: These tumors have a gene expression profile reminiscent of nonmalignant "normal" breast epithelium. Prognosis is similar to the luminal B group.
HER2 amplified: These tumors have amplification of the HER2 gene on chromosome 17q and frequently exhibit coamplification and overexpression of other genes adjacent to HER2. Historically, the clinical prognosis of such tumors was poor. However, with the advent of trastuzumab, the clinical outcome of HER2-positive patients is markedly improving.
Basal: These ER/progesterone receptor-negative and HER2-negative tumors (so-called triple negative) are characterized by markers of basal/myoepithelial cells. They tend to be high grade, and express cytokeratins 5/6 and 17 as well as vimentin, p63, CD10, α-smooth muscle actin, and epidermal growth factor receptor (EGF-R). Patients with BRCA mutations also fall within this molecular subtype. They also have stem cell characteristics.
PRIMARY BREAST CANCER Breast-conserving treatments, consisting of the removal of the primary tumor by some form of lumpectomy with or without irradiating the breast, result in a survival that is as good as (or slightly superior to) that after extensive surgical procedures, such as mastectomy or modified radical mastectomy, with or without further irradiation. Postlumpectomy breast irradiation greatly reduces the risk of recurrence in the breast. While breast conservation is associated with a possibility of recurrence in the breast, 10-year survival is at least as good as that after more extensive surgery. Postoperative radiation to regional nodes following mastectomy is also associated with an improvement in survival. Since radiation therapy can also reduce the rate of local or regional recurrence, it should be strongly considered following mastectomy for women with high-risk primary tumors (i.e., T2 in size, positive margins, positive nodes). At present, nearly one-third of women in the United States are managed by lumpectomy. Breast-conserving surgery is not suitable for all patients: it is not generally suitable for tumors >5 cm (or for smaller tumors if the breast is small), for tumors involving the nipple areola complex, for tumors with extensive intraductal disease involving multiple quadrants of the breast, for women with a history of collagen vascular disease, and for women who either do not have the motivation for breast conservation or do not have convenient access to radiation therapy. However, these groups probably do not account for more than one-third of patients who are treated with mastectomy. Thus, a great many women still undergo mastectomy who could safely avoid this procedure and probably would if appropriately counseled.
An extensive intraductal component is a predictor of recurrence in the breast, and so are several clinical variables. Both axillary lymph node involvement and involvement of vascular or lymphatic channels by metastatic tumor in the breast are associated with a higher risk of relapse in the breast but are not contraindications to breast-conserving treatment. When these patients are excluded and when lumpectomy with negative tumor margins is achieved, breast conservation is associated with a recurrence rate in the breast of substantially <10%. The survival rate of patients who have recurrence in the breast is somewhat worse than that of women who do not. Thus, recurrence in the breast is a negative prognostic variable for long-term survival. However, recurrence in the breast is not the cause of distant metastasis. If recurrence in the breast caused metastatic disease, then women treated with lumpectomy, who have a higher rate of recurrence in the breast, should have poorer survival rate than women treated with mastectomy, and they do not. Most patients should consult with a radiation oncologist before making a final decision concerning local therapy. However, a multimodality clinic in which the surgeon, radiation oncologist, medical oncologist, and other caregivers cooperate to evaluate the patient and develop a treatment is usually considered a major advantage by patients.
Adjuvant Therapy The use of systemic therapy after local management of breast cancer substantially improves survival. More than half of the women who would otherwise die of metastatic breast cancer remain disease-free when treated with the appropriate systemic regimen. These data have grown more and more impressive with longer follow-up and more effective regimens.
Prognostic Variables The most important prognostic variables are provided by tumor staging. The size of the tumor and the status of the axillary lymph nodes provide reasonably accurate information on the likelihood of tumor relapse. The relation of pathologic stage to 5-year survival is shown in Table 37-2. For most women, the need for adjuvant therapy can be readily defined on this basis alone. In the absence of lymph node involvement, involvement of microvessels (either capillaries or lymphatic channels) in tumors is nearly equivalent to lymph node involvement. The greatest controversy concerns women with intermediate prognoses. There is rarely justification for adjuvant chemotherapy in most women with tumors <1 cm in size whose axillary lymph nodes are negative. HER2-positive tumors are a potential exception. Detection of breast cancer cells either in the circulation or bone marrow is associated with an increased relapse rate. The most exciting development in this area is the use of gene expression arrays to analyze patterns of tumor gene expression. Several groups have independently defined gene sets that reliably predict disease-free and overall survival far more accurately than any single prognostic variable, including the Oncotype DX analysis of 21 genes. Also, the use of such standardized risk assessment tools such as Adjuvant! Online (www.adjuvantonline.com) is very helpful. These tools are highly recommended in otherwise ambiguous circumstances. Estrogen and progesterone receptor status are of prognostic significance. Tumors that lack either or both of these receptors are more likely to recur than tumors that have them.
Several measures of tumor growth rate correlate with early relapse. S-phase analysis using flow cytometry is the most accurate measure. Indirect S-phase assessments using antigens associated with the cell cycle, such as PCNA (Ki67), are also valuable. Tumors with a high proportion (more than the median) of cells in S-phase pose a greater risk of relapse; chemotherapy offers the greatest survival benefit for these tumors. Assessment of DNA content in the form of ploidy is of modest value, with nondiploid tumors having a somewhat worse prognosis.
Histologic classification of the tumor has also been used as a prognostic factor. Tumors with a poor nuclear grade have a higher risk of recurrence than tumors with a good nuclear grade. Semiquantitative measures such as the Elston score improve the reproducibility of this measurement.
Molecular changes in the tumor are also useful. Tumors that overexpress erbB2 (HER2/neu) or have a mutated p53 gene have a worse prognosis. Particular interest has centered on erbB2 overexpression as measured by histochemistry or by fluorescence in situ hybridization. Tumors that overexpress erbB2 are more likely to respond to higher doses of doxorubicin-containing regimens and predict those tumors that will respond to HER2/neu antibodies (trastuzumab) (herceptin) and HER2/neu kinase inhibitors.
To grow, tumors must generate a neovasculature (Chap. 25). The presence of more microvessels in a tumor, particularly when localized in so-called hot spots, is associated with a worse prognosis. This may assume even greater significance in light of blood vessel–targeting therapies such as bevacizumab (avastin). While the benefits of bevacizumab in metastatic disease have been modest, close attention should be paid to the soon-to-be reported studies evaluating its role in adjuvant therapy.
Other variables that have also been used to evaluate prognosis include proteins associated with invasiveness, such as type IV collagenase, cathepsin D, plasminogen activator, plasminogen activator receptor, and the metastasis-suppressor gene nm23. None of these has been widely accepted as a prognostic variable for therapeutic decision-making. One problem in interpreting these prognostic variables is that most of them have not been examined in a study using a large cohort of patients.
Adjuvant Regimens Adjuvant therapy is the use of systemic therapies in patients whose known disease has received local therapy but who are at risk of relapse. Selection of appropriate adjuvant chemotherapy or hormone therapy is highly controversial in some situations. Meta-analyses have helped to define broad limits for therapy but do not help in choosing optimal regimens or in choosing a regimen for certain subgroups of patients. A summary of recommendations is shown in Table 37-3. In general, premenopausal women for whom any form of adjuvant systemic therapy is indicated should receive multidrug chemotherapy. Antihormone therapy improves survival in premenopausal patients with positive ER and should be added following completion of chemotherapy. Prophylactic castration may also be associated with a substantial survival benefit (primarily in ER-positive patients) but is not widely used in this country.
Data on postmenopausal women are also controversial. The impact of adjuvant chemotherapy is quantitatively less clear-cut than in premenopausal patients, particularly in ER-positive cases, although survival advantages have been shown. The first decision is whether chemotherapy or endocrine therapy should be used. While adjuvant endocrine therapy (aromatase inhibitors and tamoxifen) improves survival regardless of axillary lymph node status, the improvement in survival is modest for patients in whom multiple lymph nodes are involved. For this reason, it has been usual to give chemotherapy to postmenopausal patients who have no medical contraindications and who have more than one positive lymph node; hormone therapy is commonly given subsequently. For postmenopausal women for whom systemic therapy is warranted but who have a more favorable prognosis (based more commonly on analysis such as the Oncotype DX methodology), hormone therapy may be used alone. Large clinical trials have shown superiority for aromatase inhibitors over tamoxifen alone in the adjuvant setting. Unfortunately, the optimal plan is unclear. Tamoxifen for 5 years followed by an aromatase inhibitor, the reverse strategy, or even switching to an aromatase inhibitor after 2–3 years of tamoxifen has been shown to be better than tamoxifen alone. No valid information currently permits selection among the three clinically approved aromatase inhibitors. Large clinical trials currently underway will help address these questions. Concomitant use of bisphosphonates is almost always warranted; however, it is not finally settled as to whether their prophylactic use increases survival in addition to just decreasing recurrences in bone.
Most comparisons of adjuvant chemotherapy regimens show little difference among them, although small advantages for doxorubicin-containing regimens and "dose-sense" regimens are usually seen.
One approach—so-called neoadjuvant chemotherapy—involves the administration of adjuvant therapy before definitive surgery and radiation therapy. Because the objective response rates of patients with breast cancer to systemic therapy in this setting exceed 75%, many patients will be "down-staged" and may become candidates for breast-conserving therapy. However, overall survival has not been improved using this approach. Patients who achieve a pathologic complete remission after neoadjuvant chemotherapy not unexpectedly have a substantially improved survival. The neoadjuvant setting also provides a wonderful opportunity for the evaluation of new agents.
Other adjuvant treatments under investigation include the use of taxanes, such as paclitaxel and docetaxel, and therapy based on alternative kinetic and biologic models. In such approaches, high doses of single agents are used separately in relatively dose-intensive cycling regimens. Node-positive patients treated with doxorubicin–cyclophosphamide for four cycles followed by four cycles of a taxane have a substantial improvement in survival as compared with women receiving doxorubicin–cyclophosphamide alone, particularly in women with ER-negative tumors. In addition, administration of the same drug combinations at the same dose but at more frequent intervals (q2 weeks with cytokine support compared with the standard q3 weeks) is even more effective. Among the 25% of women whose tumors overexpress HER2/neu, addition of trastuzumab given concurrently with a taxane and then for 1 year after chemotherapy produces significant improvement in survival. Though longer follow-up will be important, this is now the standard care for most women with HER2/neu—positive breast cancers. Cardiotoxicity, immediate and long term, remains a concern, and further efforts to exploit non—anthracycline-containing regimens are being pursued. Very-high-dose therapy with stem cell transplantation in the adjuvant setting has not proved superior to standard-dose therapy and should not be routinely used.
A variety of exciting approaches are close to adoption, and the literature needs to be followed attentively. These include the use of antiangiogenics such as bevacizumab. In addition, tyrosine kinase inhibitors such as lapatinib that target the HER2 kinase are very promising. Finally, as described in the next section, a novel class of agents targeting DNA repair—the so-called poly—ADP ribose polymerase (PARP) inhibitors—is likely to have a major impact on breast cancers either caused by BRCA-1 or -2 mutations or sharing similar defects in DNA repair in their etiology.
SYSTEMIC THERAPY OF METASTATIC DISEASE About one-third of patients treated for apparently localized breast cancer develop metastatic disease. Although a small number of these patients enjoy long remissions when treated with combinations of systemic and local therapy, most eventually succumb to metastatic disease. The median survival time for all patients diagnosed with mestastatic breast cancer is less than 3 years. Soft tissue, bony, and visceral (lung and liver) metastases each account for approximately one-third of sites of initial relapses. However, by the time of death, most patients will have bony involvement. Recurrences can appear at any time after primary therapy. A very cruel fact about breast cancer recurrences is that at least half of all breast cancer recurrences occur >5 years after initial therapy.
Because the diagnosis of metastatic disease alters the outlook for the patient so drastically, it should rarely be made without a confirmatory biopsy. Every oncologist has seen patients with tuberculosis, gallstones, sarcoidosis, or other nonmalignant diseases misdiagnosed and treated as though they had metastatic breast cancer or even second malignancies such as multiple myeloma thought to be recurrent breast cancer. This is a catastrophic mistake and justifies biopsy for virtually every patient at the time of initial suspicion of metastatic 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 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. 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.
In many cases, systemic therapy can be withheld while the patient is managed with appropriate local therapy. Radiation therapy and occasionally surgery are effective at relieving the symptoms of metastatic disease, particularly when bony sites are involved. Many patients with bone-only or bone-dominant disease have a relatively indolent course. Under such circumstances, systemic chemotherapy has a modest effect, whereas radiation therapy may be effective for long periods. Other systemic treatments, such as strontium 89 and/or bisphosphonates, may provide a palliative benefit without inducing objective responses. Most patients with metastatic disease, and certainly all who have bone involvement, should receive concurrent bisphosphonates. Since the goal of therapy is to maintain well-being for as long as possible, emphasis should be placed on avoiding the most hazardous complications of metastatic disease, including pathologic fracture of the axial skeleton and spinal cord compression. New back pain in patients with cancer should be explored aggressively on an emergent basis; to wait for neurologic symptoms is a potentially catastrophic error. Metastatic involvement of endocrine organs can cause profound dysfunction, including adrenal insufficiency and hypopituitarism. Similarly, obstruction of the biliary tree or other impaired organ function may be better managed with a local therapy than with a systemic approach.
Endocrine Therapy Normal breast tissue is estrogen dependent. Both primary and metastatic breast cancer may retain this phenotype. The best means of ascertaining whether a breast cancer is hormone dependent is through analysis of estrogen and progesterone receptor levels on the tumor. Tumors that are positive for the ER and negative for the progesterone receptor have a response rate of ~30%. Tumors that have both receptors have a response rate approaching 70%. If neither receptor is present, the objective response rates are <5%. Receptor analyses provide information as to the correct ordering of endocrine therapies as opposed to chemotherapy. Because of their lack of toxicity and because some patients whose receptor analyses are reported as negative respond to endocrine therapy, an endocrine treatment should be attempted in virtually every patient with metastatic breast cancer. Potential endocrine therapies are summarized in Table 37-4. The choice of endocrine therapy is usually determined by toxicity profile and availability. In most patients, the initial endocrine therapy should be an aromatase inhibitor rather than tamoxifen. For the subset of postmenopausal women who are ER positive but also HER2/neu positive, response rates to aromatase inhibitors are substantially higher than to tamoxifen. Newer "pure" antiestrogens that are free of agonistic effects are also effective. Cases in which tumors shrink in response to tamoxifen withdrawal (as well as withdrawal of pharmacologic doses of estrogens) have been reported. Endogenous estrogen formation may be blocked by analogues of luteinizing hormone–releasing hormone in premenopausal women. Additive endocrine therapies, including treatment with progestogens, estrogens, and androgens, may also be tried in patients who respond to initial endocrine therapy; the mechanism of action of these latter therapies is unknown. Patients who respond to one endocrine therapy have at least a 50% chance of responding to a second endocrine therapy. It is not uncommon for patients to respond to two or three sequential endocrine therapies; however, combination endocrine therapies do not appear to be superior to individual agents, and combinations of chemotherapy with endocrine therapy are not useful. The median survival time of patients with metastatic disease is approximately 2 years, and many patients, particularly older persons and those with hormone-dependent disease, may respond to endocrine therapy for 3–5 years or longer.
Chemotherapy Unlike many other epithelial malignancies, breast cancer responds to multiple 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 effect on duration of response or survival. 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. No method 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. One randomized study has suggested docetaxel may be superior to paclitaxel. A nanoparticle formulation of paclitaxel (Abraxane) is also effective.
The use of a humanized antibody to erbB2 (trastuzumab [Herceptin]) combined with paclitaxel can improve response rate and survival for women whose metastatic tumors overexpress erbB2. The magnitude of the survival extension is modest in patients with metastatic disease. Similarly, the use of bevacizumab (avastin) has improved the response rate and response duration to paclitaxel. Objective responses in previously treated patients may also be seen with gemcitabine, vinca alkaloids, capecitabine, Navelbine, and oral etoposide and a new class of agents (epothilones).
High-Dose Chemotherapy Including Autologous Bone Marrow Transplantation Autologous bone marrow transplantation combined with high doses of single agents can produce objective responses even in heavily pretreated patients. However, such responses are rarely durable and do not alter the clinical course for most patients with advanced metastatic disease.
STAGE III BREAST CANCER Between 10 and 25% of patients present with so-called locally advanced, or stage III, breast cancer at diagnosis. Many of these cancers are technically operable, whereas others, particularly cancers with chest wall involvement, inflammatory breast cancers, or cancers with large matted axillary lymph nodes, cannot be managed with surgery initially. Although no randomized trials have proved the efficacy of neoadjuvant 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. These patients should be managed in multimodality clinics to coordinate surgery, radiation therapy, and systemic chemotherapy. Such approaches produce long-term disease-free survival in about 30–50% of patients.
BREAST CANCER PREVENTION Women who have one breast cancer are at risk of developing a contralateral breast cancer at a rate of approximately 0.5% per year. When adjuvant tamoxifen is administered to these patients, the rate of development of contralateral breast cancers is reduced. In other tissues of the body, tamoxifen has estrogen-like effects that are beneficial: preservation of bone mineral density and long-term lowering of cholesterol. However, tamoxifen has estrogen-like effects on the uterus, leading to an increased risk of uterine cancer (0.75% incidence after 5 years on tamoxifen). Tamoxifen also increases the risk of cataract formation. The Breast Cancer Prevention Trial (BCPT) revealed a >49% reduction in breast cancer among women with a risk of at least 1.66% taking the drug for 5 years. Raloxifene has shown similar breast cancer prevention potency but may have different effects on bone and heart. The two agents have been compared in a prospective randomized prevention trial (the Study of Tamoxifen and Raloxifene [STAR] trial). The agents are approximately equivalent in preventing breast cancer with fewer thromboembolic events and endometrial cancers with raloxifene; however, raloxifene did not reduce noninvasive cancers as effectively as tamoxifen, so no clear winner has emerged. A newer selective estrogen receptor modulator (SERM), lasofoxifene, has recently been shown to reduce cardiovascular events in addition to breast cancer and fractures, and further studies of this agent should be watched with interest. It should be recalled that prevention of contralateral breast cancers in women diagnosed with onc cancer is a reasonable surrogate for breast cancer prevention as these are second primaries not recurrences. In this regard, the aromatase inhibitors are all considerably more effective than tamoxifen; however, they are not approved for primary breast cancer prevention. It remains puzzling that agents with the safety profile of raloxifene, which can reduce breast cancer risk by 50% with additional benefits in preventing osteoporotic fracture, are still so infrequently prescribed.
NONINVASIVE BREAST CANCER Breast cancer develops as a series of molecular changes in the epithelial cells that lead to ever more malignant behavior. Increased use of mammography has led to more frequent diagnoses of noninvasive breast cancer. These lesions fall into two groups: ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (lobular neoplasia). The management of both entities is controversial.
Ductal Carcinoma In Situ Proliferation of cytologically malignant breast epithelial cells within the ducts is termed DCIS. Atypical hyperplasia may be difficult to differentiate from DCIS. At least one-third of patients with untreated DCIS develop invasive breast cancer within 5 years. For many years, the standard treatment for this disease was mastectomy. However, treatment of this condition by lumpectomy and radiation therapy gives survival that is as good as the survival for invasive breast cancer treated by mastectomy. In one randomized trial, the combination of wide excision plus irradiation for DCIS caused a substantial reduction in the local recurrence rate compared with wide excision alone with negative margins, though survival was identical in the two arms. No studies have compared either of these regimens with mastectomy. Addition of tamoxifen to any DCIS surgical/radiation therapy regimen further improves local control. Data for aromatase inhibitors in this setting are not available.
Several prognostic features may help to identify patients at high risk for local recurrence after either lumpectomy alone or lumpectomy with radiation therapy. These include extensive disease; age <40 years; and cytologic features such as necrosis, poor nuclear grade, and comedo subtype with overexpression of erbB2. Some data suggest that adequate excision with careful determination of pathologically clear margins is associated with a low recurrence rate. When surgery is combined with radiation therapy, recurrence (which is usually in the same quadrant) occurs with a frequency of ≤10%. Given the fact that half of these recurrences will be invasive, about 5% of the initial cohort will eventually develop invasive breast cancer. A reasonable expectation of mortality for these patients is about 1%, a figure that approximates the mortality rate for DCIS managed by mastectomy. Although this train of reasoning has not formally been proved valid, it is reasonable to recommend that patients who desire breast preservation, and in whom DCIS appears to be reasonably localized, be managed by adequate surgery with meticulous pathologic evaluation, followed by breast irradiation and tamoxifen. For patients with localized DCIS, axillary lymph node dissection is unnecessary. More controversial is the question of what management is optimal when there is any degree of invasion. Because of a significant likelihood (10–15%) of axillary lymph node involvement even when the primary lesion shows only microscopic invasion, it is prudent to do at least a level 1 and 2 axillary lymph node dissection for all patients with any degree of invasion, or sentinel node biopsy may be substituted. Further management is dictated by the presence of nodal spread.
Lobular Neoplasia Proliferation of cytologically malignant cells within the lobules is termed lobular neoplasia. Nearly 30% of patients who have had adequate local excision of the lesion develop breast cancer (usually infiltrating ductal carcinoma) over the next 15–20 years. Ipsilateral and contralateral cancers are equally common. Therefore, lobular neoplasia may be a premalignant lesion that suggests an elevated risk of subsequent breast cancer rather than a form of malignancy itself, and aggressive local management seems unreasonable. Most patients should be treated with an SERM for 5 years and followed with careful annual mammography and semiannual physical examinations. Additional molecular analysis of these lesions may make it possible to discriminate between patients who are at risk of further progression and require additional therapy and those in whom simple follow-up is adequate.
MALE BREAST CANCER Breast cancer is about 1/150th as frequent in men as in women; 1720 men developed breast cancer in 2006. It usually presents as a unilateral lump in the breast and is frequently not diagnosed promptly. Given the small amount of soft tissue and the unexpected nature of the problem, locally advanced presentations are somewhat more common. When male breast cancer is matched to female breast cancer by age and stage, its overall prognosis is identical. Although gynecomastia may initially be unilateral or asymmetric, any unilateral mass in a man older than age 40 years should receive a careful workup, including biopsy. On the other hand, bilateral symmetric breast development rarely represents breast cancer and is almost invariably due to endocrine disease or a drug effect. It should be kept in mind, nevertheless, that the risk of cancer is much greater in men with gynecomastia; in such men, gross asymmetry of the breasts should arouse suspicion of cancer. Male breast cancer is best managed by mastectomy and axillary lymph node dissection (modified radical mastectomy). Patients with locally advanced disease or positive nodes should also be treated with irradiation. Approximately 90% of male breast cancers contain ERs, and approximately 60% of cases with metastatic disease respond to endocrine therapy. No randomized studies have evaluated adjuvant therapy for male breast cancer. Two historic experiences suggest that the disease responds well to adjuvant systemic therapy, and, if not medically contraindicated, the same criteria for the use of adjuvant therapy in women should be applied to men.
The sites of relapse and spectrum of response to chemotherapeutic drugs are virtually identical for breast cancers in either sex.
Follow-Up of Breast Cancer Patients Despite the availability of sophisticated and expensive imaging techniques and a wide range of serum tumor marker tests, survival is not influenced by early diagnosis of relapse. Surveillance guidelines are given in Table 37-5. Despite pressure from patients and their families, routine computed tomography and so on are not recommended.