Carcinoma of the Female Breast
Essentials of Diagnosis
- Most women with breast cancer do not have identifiable risk factors.
- Risk factors include delayed childbearing, positive family history of breast cancer or genetic mutations (BRCA1, BRCA2), and personal history of breast cancer or some types of proliferative conditions.
- Early findings: Single, nontender, firm to hard mass with ill-defined margins; mammographic abnormalities and no palpable mass.
- Later findings: Skin or nipple retraction; axillary lymphadenopathy; breast enlargement, erythema, edema, pain; fixation of mass to skin or chest wall.
Incidence & Risk Factors
Breast cancer will develop in one of eight American women. Next to skin cancer, breast cancer is the most common cancer in women; it is second only to lung cancer as a cause of death. The probability of developing breast cancer increases throughout life. The mean and the median age of women with breast cancer is between 60 and 61 years.
There will be about 178,000 new cases of breast cancer and about 41,000 deaths from this disease in women in the United States in 2007. An additional 62,000 cases of ductal carcinoma in situ will be detected, principally by screening mammography. The incidence of breast cancer has slightly decreased, presumably because of decreased use of postmenopausal hormone replacement therapy. Mortality has also decreased slightly due to early detection and increased use of systemic therapy.
Although more than 75% of women in whom breast cancer has been diagnosed do not have an obvious risk factor, there are several that play a role in breast cancer development. Breast cancer is three to four times more likely to develop in women with a first-degree relative (mother, daughter, or sister) who had breast cancer than in those without a family history. Risk is further increased in patients whose mothers' or sisters' breast cancers occurred before menopause or were bilateral and in those with a family history of breast cancer in two or more first-degree relatives as well as in women of Ashkenazi Jewish descent. Nulliparous women and women whose first full-term pregnancy was after age 35 have a 1.5 times higher incidence of breast cancer than multiparous women. Late menarche and artificial menopause are associated with a lower incidence, whereas early menarche (under age 12) and late natural menopause (after age 50) are associated with a slight increase in risk. Fibrocystic condition, when accompanied by proliferative changes, papillomatosis, or atypical epithelial hyperplasia, and increased breast density on mammogram are also associated with an increased incidence. A woman who had cancer in one breast is at increased risk for cancer developing in the other breast. In these women, a contralateral cancer develops at the rate of 1% or 2% per year. Women with cancer of the uterine corpus have a risk of breast cancer significantly higher than that of the general population, and women with breast cancer have a comparably increased risk for endometrial cancer. In the United States, breast cancer is more common in white women. The incidence of the disease among nonwhite (mostly black) women is increasing, especially in younger women. In general, rates reported from developing countries are low, whereas rates are high in developed countries, with the notable exception of Japan. Some of the variability may be due to underreporting in the developing countries, but a real difference probably exists. Dietary factors, particularly increased fat consumption, may account for some differences in incidence. Oral contraceptives do not appear to increase the risk of breast cancer. There is evidence that administration of estrogens to postmenopausal women may result in a slightly increased risk of breast cancer, but only with higher, long-term doses of estrogens. Concomitant administration of progesterone and estrogen may markedly increase the incidence of breast cancer compared with the use of estrogen alone. The Women's Health Initiative prospective randomized study of hormone replacement therapy stopped treatment with estrogen and progesterone early because of an increased risk of breast cancer compared with untreated controls or women treated with estrogen alone. With decreasing use of these hormones, breast cancer rates may continue to decrease. Alcohol consumption increases the risk slightly.
Some inherited breast cancers have been found to be associated with a gene on chromosome 17. This gene, BRCA1, is mutated in families with early-onset breast and ovarian cancer. Breast cancer will develop in approximately 85% of women with BRCA1 gene mutations during their lifetime. Other genes are associated with increased risk of breast and other cancers, such as BRCA2 (associated with a gene on chromosome 13); ataxia-telangiectasia mutation; and mutation of p53, the tumor suppressor gene. Mutations to p53 have been found in approximately 1% of breast cancers in women under 40 years of age. Genetic testing is commercially available for women at high risk for breast cancer. Women with genetic mutations in whom breast cancer develops may be treated in the same way as women who do not have mutations (ie, lumpectomy), though data are emerging to suggest an increased recurrence rate for these women. Such women with mutations often elect bilateral mastectomy as treatment. Some states have enacted legislation to prevent insurance companies from considering mutations as "preexisting conditions," preventing insurability.
Women at greater than normal risk for developing breast cancer (Table 16–1) should be identified by their practitionersand monitored carefully. Those with an exceptional family history should be counseled about the option of genetic testing. Some of these high-risk women may consider prophylactic mastectomy, oophorectomy, or tamoxifen, an FDA-approved preventive agent.
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Prevention
The National Surgical Adjuvant Breast Project (NSABP) conducted the first Breast Cancer Prevention Trial (BCPT) P-1, which evaluated tamoxifen as a preventive agent in women with no personal history of breast cancer but at high risk for developing the disease. Women who received tamoxifen for 5 years had about a 50% reduction in noninvasive and invasive cancers compared with women taking placebo. However, women over age 50 who received the drug had an increased incidence of endometrial cancer and deep venous thrombosis. Unfortunately, no survival data will be produced from this trial because it was stopped.
The selective estrogen receptor modulator (SERM) raloxifene, effective in preventing osteoporosis, is also effective in preventing breast cancer. The initial study, Multiple Outcomes of Raloxifene Evaluations (MORE) trial, aimed at determining the effect of raloxifene on bone, demonstrated that raloxifene also reduced breast cancer risk in women being given the drug. After 8 years, raloxifene demonstrated an overall reduction of invasive breast cancer of 66%. Because this study was designed to determine the effect of raloxifene on bone density, it was conducted in women at lower risk for breast cancer. To better understand the preventive effect of raloxifene in the high-risk population, a randomized study comparing raloxifene with tamoxifen was conducted.
The Study of Tamoxifen and Raloxifene (STAR) P-2 trial, conducted by the NSABP and completed in 2006, demonstrated that raloxifene and tamoxifen are equivalent in preventing invasive breast cancer in the high-risk population. Many of the side effects of raloxifene are the same as tamoxifen with a slight decrease in cataracts and thromboembolic events in the raloxifene group.
Similar to SERMs, aromatase inhibitors (AI) have shown great success in treating breast cancer with fewer side effects, although bone loss is a significant side effect of this long-term treatment. Several large multicenter studies (eg, International Breast Cancer Intervention Study II [IBIS-II] and National Cancer Institute of Canada Clinical Trials Group [NCIC CTG] are underway to determine whether AIs have a role in preventing breast cancer.
In addition to pharmaceutical therapy, patients continue to seek a way to prevent breast cancer. There has been considerable research on incorporating diet and exercise into the lifestyle of women who may be at risk for cancer. The Women's Intervention Nutrition Study was conducted to determine whether decreasing dietary fat intake would reduce the incidence of breast cancer recurrence after initial treatment. Although the trial demonstrated a decrease in recurrence in the follow-up period, it did not reach statistical significance.
Early Detection of Breast Cancer
Screening Programs
There have been a number of large screening programs conducted over the years. Such programs, consisting of physical and mammographic examination of asymptomatic women, identify about 10 cancers per 1000 women over the age of 50 and about 2 cancers per 1000 women under the age of 50. These studies show the increased survival benefit of screening programs, as screening detects cancer before it has spread to the lymph nodes in about 80% of the women evaluated. This increases the chance of survival to about 85% at 5 years.
Both physical examination and mammography are necessary for maximum yield in screening programs, since about 35–50% of early breast cancers can be discovered only by mammography and another 40% can be detected only by palpation.
About one-third of the abnormalities detected on screening mammograms will be found to be malignant when biopsy is performed. The probability of cancer on a screening mammogram is directly related to the Breast Imaging and Reporting Data System (BIRADS) assessment, and work-up should be performed based on this classification. Women 20–40 years of age should have a breast examination as part of routine medical care every 2–3 years. Women over age 40 years should have annual breast examinations.
The sensitivity of mammography varies from approximately 60% to 90%. This sensitivity depends on several factors, including patient age (breast density) and tumor size, location, and mammographic appearance. In young women with dense breasts (see x-ray), mammography is less sensitive than in older women with fatty breasts, in whom mammography can detect at least 90% of malignancies (see x-ray). Smaller tumors, particularly those without calcifications, are more difficult to detect, especially in dense breasts. The lack of sensitivity and the low incidence of breast cancer in young women have led to questions concerning the value of mammography for screening in women 40–50 years of age. The specificity of mammography in women under 50 years varies from about 30% to 40% for nonpalpable mammographic abnormalities to 85% to 90% for clinically evident malignancies
Carcinoma of the Female Breast
Essentials of Diagnosis
- Most women with breast cancer do not have identifiable risk factors.
- Risk factors include delayed childbearing, positive family history of breast cancer or genetic mutations (BRCA1, BRCA2), and personal history of breast cancer or some types of proliferative conditions.
- Early findings: Single, nontender, firm to hard mass with ill-defined margins; mammographic abnormalities and no palpable mass.
- Later findings: Skin or nipple retraction; axillary lymphadenopathy; breast enlargement, erythema, edema, pain; fixation of mass to skin or chest wall.
Incidence & Risk Factors
Breast cancer will develop in one of eight American women. Next to skin cancer, breast cancer is the most common cancer in women; it is second only to lung cancer as a cause of death. The probability of developing breast cancer increases throughout life. The mean and the median age of women with breast cancer is between 60 and 61 years.
There will be about 178,000 new cases of breast cancer and about 41,000 deaths from this disease in women in the United States in 2007. An additional 62,000 cases of ductal carcinoma in situ will be detected, principally by screening mammography. The incidence of breast cancer has slightly decreased, presumably because of decreased use of postmenopausal hormone replacement therapy. Mortality has also decreased slightly due to early detection and increased use of systemic therapy.
Although more than 75% of women in whom breast cancer has been diagnosed do not have an obvious risk factor, there are several that play a role in breast cancer development. Breast cancer is three to four times more likely to develop in women with a first-degree relative (mother, daughter, or sister) who had breast cancer than in those without a family history. Risk is further increased in patients whose mothers' or sisters' breast cancers occurred before menopause or were bilateral and in those with a family history of breast cancer in two or more first-degree relatives as well as in women of Ashkenazi Jewish descent. Nulliparous women and women whose first full-term pregnancy was after age 35 have a 1.5 times higher incidence of breast cancer than multiparous women. Late menarche and artificial menopause are associated with a lower incidence, whereas early menarche (under age 12) and late natural menopause (after age 50) are associated with a slight increase in risk. Fibrocystic condition, when accompanied by proliferative changes, papillomatosis, or atypical epithelial hyperplasia, and increased breast density on mammogram are also associated with an increased incidence. A woman who had cancer in one breast is at increased risk for cancer developing in the other breast. In these women, a contralateral cancer develops at the rate of 1% or 2% per year. Women with cancer of the uterine corpus have a risk of breast cancer significantly higher than that of the general population, and women with breast cancer have a comparably increased risk for endometrial cancer. In the United States, breast cancer is more common in white women. The incidence of the disease among nonwhite (mostly black) women is increasing, especially in younger women. In general, rates reported from developing countries are low, whereas rates are high in developed countries, with the notable exception of Japan. Some of the variability may be due to underreporting in the developing countries, but a real difference probably exists. Dietary factors, particularly increased fat consumption, may account for some differences in incidence. Oral contraceptives do not appear to increase the risk of breast cancer. There is evidence that administration of estrogens to postmenopausal women may result in a slightly increased risk of breast cancer, but only with higher, long-term doses of estrogens. Concomitant administration of progesterone and estrogen may markedly increase the incidence of breast cancer compared with the use of estrogen alone. The Women's Health Initiative prospective randomized study of hormone replacement therapy stopped treatment with estrogen and progesterone early because of an increased risk of breast cancer compared with untreated controls or women treated with estrogen alone. With decreasing use of these hormones, breast cancer rates may continue to decrease. Alcohol consumption increases the risk slightly.
Some inherited breast cancers have been found to be associated with a gene on chromosome 17. This gene, BRCA1, is mutated in families with early-onset breast and ovarian cancer. Breast cancer will develop in approximately 85% of women with BRCA1 gene mutations during their lifetime. Other genes are associated with increased risk of breast and other cancers, such as BRCA2 (associated with a gene on chromosome 13); ataxia-telangiectasia mutation; and mutation of p53, the tumor suppressor gene. Mutations to p53 have been found in approximately 1% of breast cancers in women under 40 years of age. Genetic testing is commercially available for women at high risk for breast cancer. Women with genetic mutations in whom breast cancer develops may be treated in the same way as women who do not have mutations (ie, lumpectomy), though data are emerging to suggest an increased recurrence rate for these women. Such women with mutations often elect bilateral mastectomy as treatment. Some states have enacted legislation to prevent insurance companies from considering mutations as "preexisting conditions," preventing insurability.
Women at greater than normal risk for developing breast cancer (Table 16–1) should be identified by their practitionersand monitored carefully. Those with an exceptional family history should be counseled about the option of genetic testing. Some of these high-risk women may consider prophylactic mastectomy, oophorectomy, or tamoxifen, an FDA-approved preventive agent.
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Prevention
The National Surgical Adjuvant Breast Project (NSABP) conducted the first Breast Cancer Prevention Trial (BCPT) P-1, which evaluated tamoxifen as a preventive agent in women with no personal history of breast cancer but at high risk for developing the disease. Women who received tamoxifen for 5 years had about a 50% reduction in noninvasive and invasive cancers compared with women taking placebo. However, women over age 50 who received the drug had an increased incidence of endometrial cancer and deep venous thrombosis. Unfortunately, no survival data will be produced from this trial because it was stopped.
The selective estrogen receptor modulator (SERM) raloxifene, effective in preventing osteoporosis, is also effective in preventing breast cancer. The initial study, Multiple Outcomes of Raloxifene Evaluations (MORE) trial, aimed at determining the effect of raloxifene on bone, demonstrated that raloxifene also reduced breast cancer risk in women being given the drug. After 8 years, raloxifene demonstrated an overall reduction of invasive breast cancer of 66%. Because this study was designed to determine the effect of raloxifene on bone density, it was conducted in women at lower risk for breast cancer. To better understand the preventive effect of raloxifene in the high-risk population, a randomized study comparing raloxifene with tamoxifen was conducted.
The Study of Tamoxifen and Raloxifene (STAR) P-2 trial, conducted by the NSABP and completed in 2006, demonstrated that raloxifene and tamoxifen are equivalent in preventing invasive breast cancer in the high-risk population. Many of the side effects of raloxifene are the same as tamoxifen with a slight decrease in cataracts and thromboembolic events in the raloxifene group.
Similar to SERMs, aromatase inhibitors (AI) have shown great success in treating breast cancer with fewer side effects, although bone loss is a significant side effect of this long-term treatment. Several large multicenter studies (eg, International Breast Cancer Intervention Study II [IBIS-II] and National Cancer Institute of Canada Clinical Trials Group [NCIC CTG] are underway to determine whether AIs have a role in preventing breast cancer.
In addition to pharmaceutical therapy, patients continue to seek a way to prevent breast cancer. There has been considerable research on incorporating diet and exercise into the lifestyle of women who may be at risk for cancer. The Women's Intervention Nutrition Study was conducted to determine whether decreasing dietary fat intake would reduce the incidence of breast cancer recurrence after initial treatment. Although the trial demonstrated a decrease in recurrence in the follow-up period, it did not reach statistical significance.
Early Detection of Breast Cancer
Screening Programs
See Related Guideline from CURRENT Practice Guidelines in Primary Care 2007
There have been a number of large screening programs conducted over the years. Such programs, consisting of physical and mammographic examination of asymptomatic women, identify about 10 cancers per 1000 women over the age of 50 and about 2 cancers per 1000 women under the age of 50. These studies show the increased survival benefit of screening programs, as screening detects cancer before it has spread to the lymph nodes in about 80% of the women evaluated. This increases the chance of survival to about 85% at 5 years.
Both physical examination and mammography are necessary for maximum yield in screening programs, since about 35–50% of early breast cancers can be discovered only by mammography and another 40% can be detected only by palpation. About one-third of the abnormalities detected on screening mammograms will be found to be malignant when biopsy is performed. The probability of cancer on a screening mammogram is directly related to the Breast Imaging and Reporting Data System (BIRADS) assessment, and work-up should be performed based on this classification. Women 20–40 years of age should have a breast examination as part of routine medical care every 2–3 years. Women over age 40 years should have annual breast examinations. The sensitivity of mammography varies from approximately 60% to 90%. This sensitivity depends on several factors, including patient age (breast density) and tumor size, location, and mammographic appearance. In young women with dense breasts (see x-ray), mammography is less sensitive than in older women with fatty breasts, in whom mammography can detect at least 90% of malignancies (see x-ray). Smaller tumors, particularly those without calcifications, are more difficult to detect, especially in dense breasts. The lack of sensitivity and the low incidence of breast cancer in young women have led to questions concerning the value of mammography for screening in women 40–50 years of age. The specificity of mammography in women under 50 years varies from about 30% to 40% for nonpalpable mammographic abnormalities to 85% to 90% for clinically evident malignancies
Screening recommendations for women in their 40s are based, in part, on trials from Sweden. Two trials showed a statistical advantage for screening women in their 40s, and a meta-analysis similarly revealed a statistical survival advantage for screened women with longer follow-up. The National Cancer Advisory Board recommended that women in their 40s with average risk factors have screening mammography every 1–2 years and that women at higher risk seek medical advice on when to begin screening. Studies continue to support the value of screening mammography in women over 40 years (see Table 1–9). Such women should have annual mammography and physical examination.
The beneficial effect of screening in women aged 50–69 years is undisputed and has been confirmed by all clinical trials. The efficacy of screening in older women—those older than 70 years—is inconclusive and is difficult to determine because few studies have examined this population.
Self-Examination
Breast self-exam (BSE) has not been shown to improve survival. Because of the lack of strong evidence demonstrating value, the American Cancer Society no longer recommends monthly BSE beginning at age 20 years. The recommendation is that patients be made aware of the potential benefits, limitations, and harms (increased biopsies or false-positive results) associated with BSE. Women who choose to perform BSE should be advised regarding the proper technique. Premenopausal women should perform the examination 7–8 days after the start of the menstrual period. First, breasts should be inspected before a mirror with the hands at the sides, overhead, and pressed firmly on the hips to contract the pectoralis muscles causing masses, asymmetry of breasts, and slight dimpling of the skin to become apparent. Next, in a supine position, each breast should be carefully palpated with the fingers of the opposite hand. Some women discover small breast lumps more readily when their skin is moist while bathing or showering. While BSE is not a recommended practice, patients should recognize and report any breast changes to their practitioners as it remains an important facet of proactive care.
Imaging
Mammography is the most reliable means of detecting breast cancer before a mass can be palpated. Slowly growing cancers can be identified by mammography at least 2 years before reaching a size detectable by palpation. Film screen mammography delivers less than 0.4 cGy to the mid breast per view. Although full-field digital mammography provides an easier method to maintain and review mammograms, it has not been proven that it provides better images or increases detection rates more than film mammography. In subset analysis of a large study, digital mammography seemed slightly superior in women with dense breasts. Computer-assisted detection (CAD) has not shown any increase in detection of cancers and is not routinely performed at centers with experienced mammographers.
Calcifications are the most easily recognized mammographic abnormality. The most common findings associated with carcinoma of the breast are clustered polymorphic microcalcifications. Such calcifications are usually at least five to eight in number, aggregated in one part of the breast and differing from each other in size and shape, often including branched or V- or Y-shaped configurations. There may be an associated mammographic mass density or, at times, only a mass density with no calcifications. Such a density usually has irregular or ill-defined borders and may lead to architectural distortion within the breast (see x-ray) but may be subtle and difficult to detect.
Indications for mammography are as follows:
(1) to screen at regular intervals asymptomatic women at high risk for developing breast cancer (see above); (2) to evaluate each breast when a diagnosis of potentially curable breast cancer has been made, and at yearly intervals thereafter; (3) to evaluate a questionable or ill-defined breast mass or other suspicious change in the breast; (4) to search for an occult breast cancer in a woman with metastatic disease in axillary nodes or elsewhere from an unknown primary; (5) to screen women prior to cosmetic operations or prior to biopsy of a mass, to examine for an unsuspected cancer; (6) to monitor those women with breast cancer who have been treated with breast-conserving surgery and radiation; and (7) to monitor the contralateral breast in those women with breast cancer treated with mastectomy.
Patients with a dominant or suspicious mass must undergo biopsy despite mammographic findings. The mammogram should be obtained prior to biopsy so that other suspicious areas can be noted and the contralateral breast can be evaluated. Mammography is never a substitute for biopsy because it may not reveal clinical cancer, especially in a very dense breast, as may be seen in young women with fibrocystic changes, and may not reveal medullary cancers (see x-ray).
Communication and documentation among the patient, the referring practitioner, and the interpreting physician are critical for high-quality screening and diagnostic mammography. The patient should be told about how she will receive timely results of her mammogram; that mammography does not "rule out" cancer; and that she may receive a correlative examination such as ultrasound at the mammography facility if referred for a suspicious lesion. She should also be aware of the technique and need for breast compression and that this may be uncomfortable. The mammography facility should be informed in writing by the clinician of abnormal physical examination findings. The Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guidelines strongly recommend that all mammography reports be communicated in writing to the patient and referring practitioner. MRI and ultrasound may be useful screening modalities in women who are at high risk for breast cancer but not for the general population. The sensitivity of MRI is much higher than mammography; however, the specificity is significantly lower and this results in multiple unnecessary biopsies. The increased sensitivity despite decreased specificity may be considered a reasonable trade-off for those at increased risk for developing breast cancer but not for normal-risk population. MRI is useful in women with breast implants to determine the character of a lesion present in the breast and to search for implant rupture and at times is helpful in patients with prior lumpectomy and radiation. In addition, positron emission tomography (PET) may play a role in imaging atypical lesions but only after diagnostic mammography has been performed. PET has demonstrated the ability to improve breast cancer diagnosis in small pilot studies, but the primary role remains evaluation of metastatic deposits.
Clinical Clues to Early Detection of Breast Cancer
Symptoms and Signs
The presenting complaint in about 70% of patients with breast cancer is a lump (usually painless) in the breast. About 90% of these breast masses are discovered by the patient. Less frequent symptoms are breast pain; nipple discharge; erosion, retraction, enlargement, or itching of the nipple; and redness, generalized hardness, enlargement, or shrinking of the breast. Rarely, an axillary mass or swelling of the arm may be the first symptom. Back or bone pain, jaundice, or weight loss may be the result of systemic metastases, but these symptoms are rarely seen on initial presentation.
The relative frequency of carcinoma in various anatomic sites in the breast is shown in the next Figure:
Inspection of the breast is the first step in physical examination and should be carried out with the patient sitting, arms at her sides and then overhead. Abnormal variations in breast size and contour, minimal nipple retraction, and slight edema, redness, or retraction of the skin can be identified. Asymmetry of the breasts and retraction or dimpling of the skin can often be accentuated by having the patient raise her arms overhead or press her hands on her hips to contract the pectoralis muscles. Axillary and supraclavicular areas should be thoroughly palpated for enlarged nodes with the patient sitting. Palpation of the breast for masses or other changes should be performed with the patient both seated and supine with the arm abducted (Figure 16–3: illustration). Palpation with a rotary motion of the examiner's fingers as well as a horizontal stripping motion has been recommended
Breast cancer usually consists of a nontender, firm or hard mass with poorly delineated margins (caused by local infiltration). Very small (1–2 mm) erosions of the nipple epithelium may be the only manifestation of Paget's carcinoma. Watery, serous, or bloody discharge from the nipple is an occasional early sign but is more often associated with benign disease.
A small lesion, less than 1 cm in diameter, may be difficult or impossible for the examiner to feel but may be discovered by the patient. She should always be asked to demonstrate the location of the mass; if the practitioner fails to confirm the patient's suspicions and imaging studies are normal, the examination should be repeated in 2–3 months, preferably 1–2 weeks after the onset of menses. During the premenstrual phase of the cycle, increased innocuous nodularity may suggest neoplasm or may obscure an underlying lesion (see x-ray). If there is any question regarding the nature of an abnormality under these circumstances, the patient should be asked to return after her period. Ultrasound is often valuable and mammography essential when an area is felt by the patient to be abnormal but the physician feels no mass. MRI may be considered, but the lack of specificity should be discussed by the practitioner and the patient
Metastases tend to involve regional lymph nodes, which may be palpable. One or two movable, nontender, not particularly firm axillary lymph nodes 5 mm or less in diameter are frequently present and are generally of no significance. Firm or hard nodes larger than 1 cm are typical of metastases. Axillary nodes that are matted or fixed to skin or deep structures indicate advanced disease (at least stage III). On the other hand, if the examiner thinks that the axillary nodes are involved, that impression will be borne out by histologic section in about 85% of cases. The incidence of positive axillary nodes increases with the size of the primary tumor. Noninvasive cancers (in situ) do not metastasize. Metastases are present in about 30% of patients with clinically negative nodes.
In most cases, no nodes are palpable in the supraclavicular fossa. Firm or hard nodes of any size in this location or just beneath the clavicle are suggestive of metastatic cancer and should be biopsied. Ipsilateral supraclavicular or infraclavicular nodes containing cancer indicate that the tumor is in an advanced stage (stage III or IV). Edema of the ipsilateral arm, commonly caused by metastatic infiltration of regional lymphatics, is also a sign of advanced cancer.
Laboratory Findings
A consistently elevated sedimentation rate may be the result of disseminated cancer. Liver or bone metastases may be associated with elevation of serum alkaline phosphatase. Hypercalcemia is an occasional important finding in advanced cancer of the breast. Carcinoembryonic antigen (CEA) and CA 15-3 or CA 27-29 may be used as markers for recurrent breast cancer but are not helpful in diagnosing early lesions. Many scientists are further investigating breast cancer markers through proteomics and hormone assays. These studies are ongoing and may prove to be helpful in early detection or evaluation of prognosis.
Imaging for Metastases
Chest radiographs may show pulmonary metastases. CT scanning of the liver and brain is of value only when metastases are suspected in these areas. Bone scans utilizing 99mTc-labeled phosphates or phosphonates are more sensitive than skeletal radiographs in detecting metastatic breast cancer. Bone scanning has not proved to be of clinical value as a routine preoperative test in the absence of symptoms, physical findings, or abnormal alkaline phosphatase or calcium levels. The frequency of abnormal findings on bone scan parallels the status of the axillary lymph nodes on pathologic examination. PET has been shown to be less useful than a bone scan to identify metastatic bone lesions. It is effective in soft tissue or visceral metastases in patients with signs or symptoms of metastatic disease. PET scanning combined with CT (PET-CT) is an effective screening method for detecting soft tissue metastases and is replacing CT scans.
Diagnostic Tests
Biopsy
The diagnosis of breast cancer depends ultimately on examination of tissue or cells removed by biopsy. Treatment should never be undertaken without an unequivocal histologic or cytologic diagnosis of cancer. The safest course is biopsy examination of all suspicious lesions found on physical examination or mammography, or both. About 60% of lesions clinically thought to be cancer prove on biopsy to be benign, while about 30% of clinically benign lesions are found to be malignant. These findings demonstrate the fallibility of clinical judgment and the necessity for biopsy.
All breast masses require a histologic diagnosis with one probable exception, a nonsuspicious, presumably fibrocystic mass, in a premenopausal woman. Rather, these masses can be observed through one or two menstrual cycles. However, if the mass does not completely resolve during this time, it must be biopsied. Figures 16-4: illustration and 16-5: illustration present algorithms for management of breast masses in premenopausal and postmenopausal patients.
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