Patient History

The patient's history should include standard epidemiologic and reproductive information to assess the relative risk factors. Information about lumps, pain, or any changes in the breast should be obtained and correlated with physical findings. Although pain is probably the most frequent breast complaint that brings a patient to a physician's office, it is uncommonly the presenting factor in cancer. Breast cancer, especially in its early stages, is usually painless. Most breast pain is related to hormone stimulation and swelling of breast tissue (although these symptoms may draw attention to a mass that proves to be cancer). Careful questioning of the patient usually reveals that the pain is cyclic, beginning any time between ovulation and the onset of menstruation, and that commonly it is most intense a few days before menstruation. Pain usually disappears by the first or second day of the menstrual period, only to return again at the next cycle. Frequently, patients complain of radiation toward the shoulder and arm; and a burning sensation that goes with constantly increased muscle tone can be attributed to subconscious muscle tension in this region. Cyclic pain is present at a mild level in more than 50% of women of childbearing age. Less frequently, the pain can reach intense proportions. Some patients report that, during the worst days, it is too painful even to take a shower.

The most effective treatment is explanation and reassurance, although some patients who are extremely symptomatic and incapacitated by the pain may require treatments with hormones or hormone-blocking drugs. There are occasional reports that caffeine limitation or low-fat diets help, but relief seems to be individual, and these reports are not supported by persuasive clinical trials.^1–3

A patient who reports a lump or any other physical change in her breast needs careful attention. The history should describe any change in the character or size of the lump and whether or not it has been tender. Pain should be described with respect to its timing in the menstrual cycle. Lumpy changes associated with a fibrocystic process may wax and wane, but it is distinctly unusual for a carcinoma to do anything but increase in size. If there is confusion, the patient should be reexamined after the menstrual period.

Other descriptive changes, such as skin thickening or discoloration, the presence of axillary masses, or nipple discharge, should be elicited. Nipple discharge may be serous, watery, or milk-like. It may be clear or have a yellow or greenish hue, or it may be serosanguineous or frankly bloody. Although the latter may indicate a neoplasm, this is most commonly an intraductal papilloma, which is benign. It is possible, but rare, for such a discharge to signal an intraductal papillary carcinoma; all bloody discharges require further investigation.

Clear or serous discharge, especially if it involves more than one major duct opening on a nipple, is likely to be benign. Non-bloody discharge that is not spontaneous but requires manual compression to elicit is also likely to be benign. In an apocrine system such as the breast, there is always some cell desquamation and liquefaction and, therefore, some fluid present in the duct system. If this is not well absorbed, it can make its way through the collecting ducts to the nipple and present as a discharge. Similarly, if the duct is blocked by fibrosis or inspissated material, the pressure of secretion can cause dilation and cyst formation. Cytologic examination of the discharge has poor accuracy and is not very useful.

Physical Examination

The patient should be examined, first in a sitting, then in a supine position. When the patient is sitting erect, more useful information is obtained visually than by palpation. When the arms are raised and stretched upward, the contour of the skin is pulled tight, allowing for easier detection of contour abnormalities in the upper half of the breast. This position also emphasizes dimpling, especially in the lower half of the breast. Because much of the breast tissue coalesces in the sitting position, it is very difficult when palpating to appreciate true masses and often easy to be confused by confluent tissue.

With the patient supine and the arm raised so that the hand is behind the head and the elbow lies flat on the pillow, the breast tissue can be spread across the chest wall, allowing for proper palpation. The patient should be slightly turned to the contralateral side to aid this process. In all but very large breasts, the tissue is now spread out across the ribs, so that there is very little tissue thickness between the examining fingers and the underlying ribs. This provides confidence that, if there is a detectable mass in this area, it will not be missed (Figure 121-16). It is important to proceed in a pattern, but whether it be by quadrants or strips is up to the examiner. The axilla is palpated by relaxing and adducting the patient's arm, but this is best done with the patient in the sitting position. Skin changes, such as dimpling, peau d'orange (edema), erythema, or areas of fixation and ulceration, suggest advanced cancer that has invaded the skin or the immediate subcutaneous tissue. Skin retraction is often more easily detected when the patient is sitting and the arms are raised or when the patient is leaning forward. The breast lobules are divided loosely into fascial compartments by Cooper's ligaments, somewhat like the divisions of a grapefruit but much less geometric. Since the fibroblastic reactions associated with cancer tend to involve and pull on these ligaments, they become shortened, and the effects can be seen on the skin with such positioning. Retraction or asymmetry of the nipple is another worrisome sign unless the patient reports that this has been present all her life. A subtle reddish thickening of the nipple may suggest Paget disease.

Figure 121-16

Changing shape of breast with position. Left, upright breast is rounded, tissues are pressed together. Right, CT scan showing breast flattening when supine. A palpable tumor is easier to detect in this position.

The examination is concluded with a search for axillary, infraclavicular, and supraclavicular nodes and palpation of the liver to detect enlargement. Although palpably enlarged axillary nodes raise the probability of metastases, careful studies have shown that clinical judgment is highly inaccurate. In a study conducted by the NSABP, a group of cancer patients were judged by their clinicians to have normal axillary nodes, but 38% showed histologic evidence of metastatic tumor when the specimens were examined pathologically.⁴ Conversely, in 25% of such cases, nodes that appeared enlarged and were judged to contain cancer were found to be normal.

The most difficult clinical decision is differentiating between a pathologic mass and a physiologic density associated with fibroglandular (or fibrocystic) changes. Many women have the latter condition, which is characterized by a rubbery density without clear margins. The process seems to blend into the surrounding breast tissue. A true lump has definite margins. Whether these are smooth, as in a gross cyst or fibroadenoma, or somewhat irregular, as in carcinoma, they delineate a discrete or dominant mass that requires further investigation. The differentiation of true masses from fibrocystic plaques is difficult to teach and is learned only with experience.

It is important to measure the size of a tumor with a caliper so that subsequent examinations can more accurately establish any change in size. Mobile lesions are usually considered benign, but this is another area of clinical uncertainty. Advanced cancers may be fixed, but early palpable lesions will certainly be mobile with respect to skin or fascia and muscle of the chest wall. There is, however, a subtle difference in mobility (better called “movability”) characteristic of cysts or fibroadenomas, which have capsules and move much more easily within the surrounding breast tissue. Carcinoma, on the other hand, which has no capsule and is surrounded by an infiltrating desmoplastic process, tends to move with the neighboring breast tissue rather than within it, because the process “locks” it into the stroma and surrounding glandular tissues, even when it is not fixed to surrounding structures, such as skin or muscle. Even the most experienced examiner can sometimes fail to distinguish correctly between benign and malignant lesions.

Screening

The refinement of x-ray methods to image the breast and the important clinical-pathologic correlations are best attributed to Gershon-Cohen in the 1940s and 1950s in Philadelphia. The use of screening mammograms in a prospective clinical trial aimed at reducing mortality by discovering preclinical breast cancers in asymptomatic women was first successfully reported by the Health Insurance Plan (HIP) study in 1975.⁵ In the trial, 31,000 women enrolled in a prepaid insurance plan were invited for screening and compared with a second group of 31,000 women in the plan who served as controls. Long-term follow-up has demonstrated a 30% reduction in mortality in favor of the screened group. The HIP study, the first of its kind, was designed to answer questions about screening among women ages 40 to 64 and does not allow for a direct answer to questions of age subsets. The study achieved its target accrual and reported that there was an overall mortality reduction from screening. The problem arises when the 40- to 49-year-old group is examined separately. This small slice of the original population was not large enough to detect a change in mortality, and the original analysis showed identical mortality for screened and control patients ages 40 to 49 at entry.⁶ Subsequently, a difference was detected for this age group, but only after 8 years of follow-up, in contrast to older women, where the difference became apparent within 4 years. Many of the women who were first screened at 40 to 49 years of age were older than 50 when their cancers were detected, a factor that raised confusion about how to interpret the results.

In analyzing screening studies, strict methodology must be observed in order to avoid bias. If tumors are found earlier by mammography than by clinical examination, the additional time gained is referred to as lead-time. If, however, the tumor has already metastasized out of the breast, the date of death will not be changed, but the length of survival from the time of diagnosis to death will be increased. This is called lead-time bias. Length bias is another, more subtle form of error that plagues this type of study. It is more likely that patients with slowly growing tumors will have their tumors detected on routine screening, whereas patients with more rapidly growing lesions (interval cancers) will be diagnosed at other times. Thus, the screened group will include more people with slower growing (more favorable biologic) tumors, and, by comparison, this group will seem to perform better.

The way to avoid these biases is simply to count the number of deaths from breast cancer in both groups. Studies that report survival rates or average survival times should be viewed with skepticism. Similarly, studies that report that screened cases had smaller tumors or earlier stages of cancer can be misleading because they may represent only lead-time biases. The use of unorthodox or unplanned-for methods of analysis can similarly lead to erroneous conclusions. The confusion surrounding age and screening benefit is a long way from becoming clear.

Early studies from Sweden and the Netherlands also demonstrated a reduced mortality for screened women who are postmenopausal.^{7, 8} None of these early studies was designed specifically to measure the impact of screening in women under the age of 50. Statistical manipulations to analyze subsets separately in these studies can sometimes show a benefit for the younger age group, but caution is required in relying on these in making final recommendations. The application of widespread screening in a group of patients where it is not useful would waste time and money and inhibit the broader application of screening in the older age group, where it is of proven benefit. The early days of the screening debate were not concerned with cost-effectiveness analyses, but the present concern with allocation of health care dollars throughout North America now makes this an important consideration. The literature on this subject can be somewhat arcane, but certain trends are emerging. Kattlove and colleagues have shown that the mortality reduction from screening is expensive, even for older women.⁹ More recently, Salzmann and associates have calculated that the cost effectiveness in screening women younger than 50 is five times more expensive than that in older women.¹⁰

To be effective, a screening program should seek a disease that is common, one whose effects are serious, and one for which a useful treatment is available. The incidence of breast cancer increases with each decade of life, but it is significantly more common in postmenopausal women so that in women under 49, more negative examinations will result and fewer cancers will be found (Table 121-3). Breast cancer is three times more likely in 55-year-old women than in 45-year-olds, and the difference is more conspicuous for wider age spreads. Furthermore, in the younger group, the breast is more glandular and, therefore, more radio-dense, raising the chance that faint signs of carcinoma will be obscured by the overlying normal tissue.

On the other hand, modern mammography equipment with high-speed film, microfocus x-ray tubes, high-speed film screen cassettes, and good selective compression techniques make the procedure more effective than it was a decade ago and increase the possibility that small carcinomas can be found in this age group. More recently, larger clinical trials have attempted to answer this question. The incidence and mortality rates of breast cancer vary by ethnicity (see Table 121-4). Many clinical features influence risk of developing breast cancer (see Table 121-5).

Role of Breast Self-Examination

In the HIP study, about one-third of breast cancer cases were found using mammography alone; overall, 75% were detectable on clinical examination.²⁵ Although mammographic techniques have improved since the 1960s, the value of clinical examination and breast self-examination (BSE) seems less clear today. Many studies have shown that women who perform regular BSEs detect breast cancers at an earlier clinical and pathologic stage of the disease, but most studies have not shown an increased chance of survival, a difference best explained by lead-time bias.

The Swedish mammography study did not include either clinical examination or BSE, which raises the question as to whether those results would have been better had these modalities been included. The Canadian NBSS included instructions in BSE, and the teaching was reinforced at subsequent annual screenings, but it is not possible to say whether the practice had any effect since all participants received instruction. It seems logical to recommend widespread use of BSE as a screening tool that is free and available to everyone, but the evidence in support of it is far from solid and remains controversial. Furthermore, the same caveats exist as for mammography. BSE can be expected to prompt a significant number of unnecessary biopsies with their attendant anxiety. It is difficult to weigh anxiety about the outcome of an unnecessary biopsy against the risk of dying of breast cancer, but that is probably not the equation in this case, since there is far less evidence that BSE reduces mortality. On the other hand, most breast masses are still self-discovered by accident, suggesting that systematic BSE could have diagnosed the disease earlier, or smaller, but the evidence is that this does not change overall mortality.

Newer studies of BSE from China have failed to demonstrate a benefit.²⁶ A meta-analysis from Canadian investigators shows no benefit of routinely teaching BSE to women and concludes that the net effect on the population is a harmful one because the potential for unnecessary biopsies and anxiety is not balanced by any gain in mortality reduction.²⁷

Differential Diagnosis

In performing breast examinations, the first objective is the detection of potential abnormalities. Discovery of an abnormality is followed by further investigation and evaluation to decide whether intervention is necessary. Thus, all abnormalities are first “caught in the net,” and then more refined tests can be performed to decide whether the findings are important enough to warrant a biopsy. The traditional clinical guidelines of mobility, smoothness, and discreteness of breast lumps are useful, but careful judgment is always required to make sure that the diagnosis of carcinoma is not missed. Such tests as mammography and ultrasound can provide additional information and should be used in most cases. Fibroadenomas cannot be easily distinguished from gross cysts clinically, but a needle aspiration solves the problem instantaneously, and both are benign. Ultrasonography can also differentiate cysts from solid lesions and is useful when mammography detects small lesions, probably cysts, that cannot be palpated.

The most common breast lumps are caused by a process previously called fibrocystic disease or mastitis. A more modern trend is to label this condition as fibrocystic or fibroglandular changes. The process is benign, usually symmetric, and most often situated in the upper outer quadrants because that is where most of the glandular tissue is found. Microscopically, there is a combination of fibrosis and ductal swelling, which gives the process its classic “fibrocystic” name. Clinically, this is a rubbery zone, but focal areas can be quite firm or hard. If a gross cyst is present, it tends to be round, circumscribed, and somewhat movable. The process is usually accompanied by pain or tenderness and tends to be cyclic, with relief as the menstrual period begins. It affects 50% of premenopausal women but usually disappears at menopause (Figure 121-17). Fibroadenomas are also smooth, round, and mobile and occur from adolescence to menopause. The British colloquial term is breast mouse, which signifies extreme mobility.

Figure 121-17

Comparative frequency of fibrocystic changes, fibroadenomas, and carcinomas by age groups.

In older women, the inferior ridge of the breast may be compressed in a crescent-shape pattern due to the weight of the overlying breast. This area represents simple fat compression and is usually benign. Many poorly defined processes require surgical biopsy to distinguish them from malignancy. Among these are sclerosing adenosis, hyperplasia with or without atypia, and mammary duct ectasia. The last is the end result of the fibrocystic process, with ducts filled with liquid and cellular debris accompanied by fibrous changes and lymphocytic infiltration.

Lesions that are less smooth and less mobile with poorly defined margins raise the suspicion of carcinoma. The identification of the nature of a mass requires careful integration of all available information, including mammography. Simple catechisms, such as “always biopsy,” are not the best guidelines. The clinician's responsibility is to establish the diagnosis of cancer when it exists but to minimize the number of unnecessary biopsies. A simplistic approach—biopsy of every clinical abnormality—would certainly identify all of the cancers but would be irresponsible, if not reckless, because of the large numbers of unnecessary operations. Similarly, abstaining from biopsy until the signs are absolutely incontrovertible would be dangerous, even though this approach would minimize unnecessary operations. The proper strategy is to apply all of the available information—history, clinical signs, mammographic and ultrasound information, and needle aspiration cytology—and to biopsy all of those lesions where a reasonable doubt as to their benign nature exists.

It is often said that mammography and needle aspiration cytology are plagued by false negatives. This view arises from an unrealistic expectation of these modalities. No single diagnostic modality is perfect, but accuracy in diagnosis improves with the integration of several tests. If the history and clinical examination suggest a benign process and a mammogram shows no abnormality, it is reasonable to integrate all of the information and use the mammogram to reinforce the clinical diagnosis of benign process. On the other hand, if the mammogram suggests suspicion for malignancy, then further steps, including biopsy, are warranted, even if the clinical examination is normal. Conversely, in a patient with a suspicious clinical mass and a normal mammogram, biopsy is necessary. Needle aspiration cytology can confirm the presence of carcinoma and allow for better planning for necessary surgery. If both the clinical and mammographic signs suggest a benign process, then a needle cytology of a fibroglandular area can add confidence to this impression and help avoid unnecessary surgery.

Diagnostic Aids: Imaging

Diagnostic Aids: Fine-Needle and Core Biopsy

Both fine-needle aspirations and core needle aspiration biopsies are very useful. Both are inexpensive, easy to perform, and require no advance preparations. In experienced hands, fine-needle aspiration yields a 90% accuracy rate.^{29, 30} Core biopsy is not always reliable for very small lesions because the spring-loaded needle can push a small tumor aside rather than penetrate it. This is not a problem in x-ray image-guided biopsy (such as the mammotome biopsy) because compression of the breast stabilizes the tissue and prevents this. For lesions larger than approximately 1 cm, core needle biopsy is an excellent office procedure to obtain clear information on the nature of the lump and to differentiate invasive from noninvasive cancer when the fine-needle aspiration shows malignancy.

Any clinically suspicious mass should be aspirated. If a mass is punctured and nonbloody fluid is aspirated with disappearance of the lump, further concern is not warranted. If the mass persists in part or in whole, or if no fluid is obtained, then cytology should be obtained on that specimen (even with no gross fluid, the same needle puncture can be used for aspiration cytology). A careful followup within a short interval is wise. If necessary, a second fine-needle aspiration can be performed.

If surgical biopsy is considered necessary, modern concepts require a definitive approach. If patients with cancer are to be successfully treated by lumpectomy, this is best accomplished at the first intervention. The suspicious mass should be excised in its entirety with a cuff of normal tissue that can be processed by the pathologist for evaluation of margins. An incisional biopsy or casual excision of a mass without such control makes it more difficult to perform a proper localized cancer operation at a subsequent time.