The occurrence of breast cancer in the contralateral breast of women with a known history of breast cancer may represent either a new primary tumor or a metastasis from the originally diagnosed breast cancer. While the determination of a new primary versus a metastasis may be difficult, a contralateral breast cancer represents a new primary if the cancer is of a different histology (e.g., ductal vs. lobular) or is associated with an in situ component. Metachronous second primary breast cancers are more likely to be in situ cancer, small size, and node negative (3). The risk of a metachronous, contralateral, second primary breast cancer is generally estimated at 0.5% to 1.0% per year (3, 4). Recent data suggests that the frequency of metachronous, contralateral, estrogen receptor positive second primary breast cancer is declining, probably because of the risk reduction provided by adjuvant endocrine therapies (5). Factors that increase the risk include a known BRCA1 or BRCA2 mutation, young age at first primary, family history of breast cancer, lobular histology for first primary breast cancer, and prior radiation exposure. Factors that decrease the risk include prior chemotherapy or endocrine therapy (6). While there are no randomized studies of screening mammography of the contralateral breast, contralateral second primary breast cancers in women undergoing routine screening mammography are smaller, and more likely to be in situ and node negative than those in women not undergoing routine mammography (7). The occurrence of metachronous contralateral breast cancer has modest impact on overall survival (7).

Conceptually, the monitoring for a new primary breast cancer in the contralateral breast may be viewed as monitoring in a high risk for breast cancer population with an increased risk of competing mortality secondary to the initial primary breast cancer. In the general population of women age 40 and older, the use of screening mammography has been demonstrated to decrease breast cancer mortality. It is thus likely that routine screening mammography would decrease breast mortality from a second primary tumor, although the mortality rate for second primary breast cancers is low.

Breast magnetic resonance imaging (MRI) screening has high sensitivity, moderate specificity, and high cost as an adjunct to the performance of mammography. No randomized clinical trials of breast MRI as screening or surveillance are available in any clinical setting. Non-randomized trials in women without known breast cancer but at high risk of breast cancer document a higher detection rate of breast cancer with the use of breast MRI scanning (8). To date, no similar prospective trial has been reported in the follow-up of women following diagnosis of breast cancer. The American Cancer Society currently recommends screening MRI as an adjunct to screening mammography, based upon non-randomized screening trials and observational studies, in women with known BRCA mutation, who have a first degree relative with a known BRCA mutation, who have a lifetime risk of greater than 20% to 25% based upon family history, who had radiation exposure to the chest between age 10 and 30 years, who have known Li-Fraumeni syndrome themselves or in first degree relatives, or who have Cowden and Bannayan-Riley-Ruvalcaba syndromes themselves or in first-degree relatives (9). The American Cancer Society makes no recommendation for or against screening MRI in women with a personal history of breast cancer. A study of breast MRI screening in women at risk of breast cancer and with negative mammograms included 245 subjects with a personal history of breast cancer (10). Breast cancers were documented in 4% of the subjects with a prior history of breast cancer, and the positive predictive value of MRI recommended biopsy was 32%. A retrospective study of women screened by MRI who had a personal, but no family, history of breast cancer documented 17 cancers in 144 subjects (11). Ten of the 17 cancers were detected by MRI only. The positive predictive value of MRI was 39%. The non-randomized nature of all of these studies prohibits assessment of the impact of breast MRI screening on breast cancer mortality.

The value of clinical breast examination has not been adequately studied, although the performance of clinical breast examination is a generally accepted part of routine healthcare of the adult female. Breast self-examination was found to be of no advantage in early detection or mortality reduction in a large, randomized clinical trial in a population of factory workers in China (12).

Based on the increased risk of a second primary breast cancer in the contralateral breast, it appears prudent to perform regular clinical breast examinations and mammography as a routine part of surveillance programs. The role of breast MRI screening is yet to be defined, but would appear reasonable in those with very high contralateral risk. Such high risk patients are those with a known, or a high risk for, genetic mutation conferring risk for breast cancer or a prior history of thoracic radiation. For other populations, insufficient information exists to allow for specific recommendations regarding the use of screening MRI. The value of breast self-examination has not been demonstrated.

Ipsilateral breast tumor recurrence following breast conserving surgery is experienced by 5 years in approximately 7% of patients with whole breast irradiation and 26% of patients without whole breast irradiation (14). The addition of a radiation boost to the tumor bed decreases in-breast recurrence rates by approximately 41% compared with whole breast irradiation alone (15). Most recurrences occur in the prior tumor bed, and positive pathologic margins, younger age, higher grade tumor, larger tumor size, negative estrogen receptor status, and involvement of axillary lymph nodes have all been reported to increase the risk of ipsilateral breast tumor recurrence (14, 15 and 16). Approximately 70% of ipsilateral breast tumor recurrences occur within the first 5 years of primary diagnosis (14, 16). Breast recurrence during the first 5 years of follow-up is associated with a substantially worse overall prognosis than are in-breast recurrences that manifest later.

Detection of ipsilateral breast tumor recurrence is often difficult because of post-surgical, post-radiotherapy changes in the breast. The sensitivity of mammography for ipsilateral breast tumor recurrences is approximately 50% to 70% and ultrasonography 80% to 85%. Overall, approximately two thirds of local recurrences are detected by the patient or on clinical examination (17, 18).Detailed reviews of studies of screening mammography in women with a personal
history of breast cancer generally document that patients diagnosed with mammography detected only in-breast recurrences have superior survival to those with symptomatic recurrences (19, 20). These studies all suffer from being relatively small in sample size and are non-randomized. Thus, it is impossible to correct for confounding by lead-time and length-time biases.

Breast MRI scanning has high sensitivity for detecting inbreast recurrences, but is expensive and is associated with highly variable specificity.

Local-regional recurrence following mastectomy is experienced by 5 years in approximately 6% of patients with postmastectomy regional irradiation and 23% of patients without postmastectomy irradiation (21). In the overview analysis, axillary lymph node status strongly predicted for absolute risk for local-regional recurrence (21). In women with axillary lymph node-negative disease, the 5-year local recurrence risk following surgery alone was 6%, and this was reduced to 2% with the use of local-regional irradiation. In women with axillary lymph node-positive disease, the 5-year local recurrence risk following surgery alone was 23% and this was reduced to 6% with the addition of local-regional irradiation. Increasing tumor grade, tumor size, and number of involved axillary lymph nodes increases the risk of local-regional recurrence.

Detection of local-regional recurrences following mastectomy with or without radiation is typically the result of either patient identification or of a routine clinical examination. Local-regional recurrences are rarely detected by radiographs or other screening studies.

Well established prognostic factors allow the estimation of risk for development of systemic disease following treatment for stage 0, I, II, and III breast cancer. Known prognostic factors include histologic subtype of breast cancer, tumor grade, tumor size, involvement of skin or chest wall, extent of involvement of regional lymph nodes, hormone receptor status, HER2 level of expression or amplification, and multigene array expression profile.

Breast cancer metastases occur in a generally predictable pattern, with synchronous multiple sites of recurrence being common. Bone is the most common site of disseminated disease, and represents approximately 40% of first recurrences. The most commonly involved bones are the spine, ribs, pelvis, skull, femur, and humerus. Breast cancer metastasis to bone distal to the elbow or knee is rare. Other common sites for metastatic disease include lung, liver, lymph nodes, and soft tissue. The site of first metastasis from breast cancer is influenced by estrogen receptor status (Table 67-1). Estrogen receptor-positive breast cancer is more likely to spread to bone, while receptor-negative breast cancer is more likely to spread to viscera and soft tissues and is associated with a higher rate of early recurrence (Table 67-1) (22, 23). Even in those patients undergoing routine surveillance during follow-up, most recurrent disease is symptomatic at time of diagnosis (24, 25).

Infiltrating lobular breast cancer has a propensity for recurrences in intra-abdominal and retroperitoneal sites including stomach, intestine, peritoneum, and ureter (often bilateral) (26).

Currently available treatment of recurrent or metastatic breast cancer is rarely curative, even when the recurrence is limited (2). Further, the amount of tumor burden in asymptomatic or minimally symptomatic patients does not predict disease response to systemic treatment, ability to palliate symptoms, or overall survival. Thus, there is no advantage to diagnosing asymptomatic, early, subclinical disease.

The routine performance of blood tests for alkaline phosphatase, aspartate aminotransferase, γ-glutamyl transferase, bilirubin, calcium, and creatinine was studied by the International Breast Cancer Study Group in 4,105 women
with invasive breast cancer (27). At the time of analysis, 2,140 patients had experienced a relapse, 93 had a second non-breast primary tumor, and 111 had died without relapse during 10-years median follow-up. In this analysis, only alkaline phosphatase was abnormal in at least 20% of patients with recurrent disease, and was abnormal in 32% of patients with bone metastasis and 71% of patients with liver metastasis. Aspartate aminotransferase and γ-glutamyl transferase were elevated in 62% and 75% of patients with liver metastasis. Bilirubin, calcium, and creatinine were of no value in detecting recurrent disease. Thus, while alkaline phosphatase was the most reliable of the blood tests, it was of low sensitivity for bone or liver disease. In another study of 1,371 patients with node positive breast cancer, serial alkaline phosphatase determinations were found to have low sensitivity and specificity for bone recurrence (28). Thus, monitoring of routine blood tests as a part of breast cancer surveillance is not recommended.