Breast Disorders and Breast Cancer Screening

Revised June 8, 2004

Pelin Batur, MD

Women's Health
Center and
Department of
General Internal
Medicine

Mark E. Mayer, MD

Department of
General Internal
Medicine

Institute for Clinical Systems Improvement

Evaluation of breast complaints and screening for breast cancer account for a significant part of primary care practice and are the dual roles of the primary physician. Complaints most frequently presented include breast pain, breast lumps, and nipple discharge. These symptoms often arise from benign conditions, but accurate evaluation is essential.

PREVALENCE

In one study, 16% of women between ages 40 and 69 came to the doctor with breast complaints over a 10-year period.¹ Estimates of the number of insured women between ages 50 and 64 getting screening mammography at least every 2 years vary from 72% to 81%;² uninsured women clearly obtain less preventive care. About 190,000 women in the United States are diagnosed with breast cancer each year. Breast cancer mortality has declined gradually over the past decade to about 40,000 per year.

PATHOPHYSIOLOGY

Most breast lumps and other breast complaints are due to benign conditions. Breast pain can be produced by fibrocystic changes, mastitis, pendulous breasts, or hidradenitis suppurativa. Chest wall pain, which may be felt as breast pain, can have many causes that do not originate in the breast. These include gallbladder disease, ischemic heart disease, trauma, intercostal neuralgia, costochondritis, and thoracic spine arthritis.

Many breast lumps are due to fibrocystic changes. Most lumps are benign, but of all complaints, they constitute the greatest proportion of symptoms leading to a diagnosis of cancer.

Nipple discharge is usually benign, especially if nonbloody, bilateral, and not spontaneous. Discharge can be due to medications, hormonal factors, prior nursing or pregnancy, or less frequently, cancer.

Risk factors for the development of breast cancer include increased age, genetic predisposition, and increased exposure to estrogen.³

Breast cancer risk is increased even if the nearest relative with breast cancer is a third-degree relative.⁴ Among women with a positive family history of breast cancer, having multiple first-degree relatives with premenopausal breast cancer confers the highest risk, a small minority of these associated with BRCA1 or BRCA2 mutations. A number of models for assessing risk of carrying a mutation have been proposed; all account for early-onset breast cancer in the family; most give weight to the number of affected relatives.⁵

Increased exposure to estrogen modestly raises the risk of breast cancer. Early menarche (before age 12) and/or late menopause (after age 55), both markers of increased estrogen exposure, confer some increased risk. The role of hormone replacement therapy (HRT) is controversial.The Women's Health Initiative, the first large scale randomized placebo-controlled trial of postmenopausal hormone use showed a 26% increased risk of breast cancer at 5.2 years in women who use combination estrogen and progestin in the form of Prempro.⁶ In contrast, women in the estrogen only arm of this trial, using Premarin, did not have any increased risk of breast cancer. The Million Women Study in the United Kingdom is the largest non-randomized study of hormone use. This study concluded that all types of hormone use, including estrogen-only forms, increased the risk of breast cancer compared to never users. The risk increased with increasing duration of use.⁷

SIGNS AND SYMPTOMS

Breast pain, breast lumps, and nipple discharge are the most common complaints presented to the physician. "Screening" is performed in the absence of symptoms; when symptoms exist, the evaluation may dictate going beyond screening procedures. In addition to a history and examination directed by the complaint, any benign disorders identified may need to be treated. If cancer is considered once the history and physical examination are done, discussions about diagnostic modalities such as imaging, aspiration, or biopsy may need to be addressed at the time of the office visit. Depending on the clinical evaluation, referral may be suggested even with pending imaging studies.

DIAGNOSIS

History:

History should include the characteristics of symptoms and their timing in relation to menstrual cycles. Breast pain is most commonly caused by fibrocystic changes. Other causes include mastitis, which usually produces sudden pain, with signs of inflammation noted. Pendulous breasts may cause pain. Hidradenitis suppurativa can present as breast nodules and pain; signs of infection, and possible concomitant involvement of the axilla should be evaluated. One should be alert for history suggesting thoracic arthritis, chest wall inflammation, breast or axillary infection, cholecystitis, or cardiac ischemia.

The presence or absence of lumps should be ascertained, and whether they wax and wane with the menstrual cycle (suggesting fibrocystic changes). Lumps associated with nipple discharge, particularly unilateral bloody discharge, are worrisome.

Symptoms of nipple discharge should be elicited. The overall rate of malignancy is low (probably around 1%). If the discharge is nonbloody, the risk of cancer is lower. Purulent discharge may be caused by mastitis or a breast abscess. Milky discharge may persist after childbearing, and can occur with some medications (see therapy section). An endocrine workup (for prolactin excess) may be needed if symptoms are sustained or associated with menstrual problems. Prior biopsies, prior treatments, and use of hormones should be ascertained.

Risk factors for cancer should be assessed whether symptoms are present or the visit is for screening only. These include age, menarche before age 12 years, menopause after age 55, and first live birth at age 30 or older. Information should be obtained about previous biopsies (whether ductal hyperplasia, and if so, whether atypical), and the number of first-degree relatives with breast cancer (and at what age their cancer was detected). The Gail Model Risk Assessment Tool may be used to help calculate risk from these history questions.⁸ A computer disk for use of the Gail model is available from the National Cancer Institute (NCI) to use in calculating this. Such estimates may aid in decision-making, particularly about chemoprevention.

Physical Examination:

There is an overall consensus that clinical breast examination (CBE) is useful in screening as well as in evaluation of a lump, although there has been debate on this issue. Four screening clinical trials included both mammography (MGM) and CBE, four others evaluated MGM only, but no trial studied CBE alone without MGM. In a comparison of studies including both screening modalities, the range of cancers detected by CBE but not by mammography was 3% to 45%. While the sensitivity of mammography is greater than that of CBE, there is a residual diagnostic value of CBE that favors its continued use in screening.⁹

Careful, systematic palpation has been shown to increase breast lump detection. Patient position, palpation of breast boundaries, and examination pattern and technique are important variables in CBE.⁹

The physical examination should include inspection and palpation. Inspection of the breasts can be done with the woman sitting with hands on her hips; some advocate inspection also with the patient sitting with her hands on top of her head, pushing downwards. The examiner looks for lumps, asymmetry or skin dimpling.

The breasts should be palpated for evaluation of texture and detection of masses. The supine patient position is preferable because CBE requires flattening breast tissue against the patient's chest, and the distance from skin to chest wall is minimized with the patient supine. The patient's ipsilateral hand should be brought up to head level for examination of the lateral aspect of the breast; the elbow should be at shoulder level for examination of the medial part of the breast.

The examination pattern should be systematic. It is important to include the area bordering the clavicle, and laterally toward the axilla, so as to ensure examination of all breast tissue. One preferred method is to start at the axilla in the midaxillary line, and to cover the breast by palpating in parallel lines, in vertical strips (the so-called lawnmower technique) to the sternum. A rectangular area bordered by the clavicle, the midsternum, the midaxillary line, and the "bra line" should be covered (Figure 1). Small, circular motions should be made at each step using the pads of the index, third, and fourth fingers, with gradated pressure (Figure 2).

Examination of the axillae for lymph nodes should follow breast examination. Examination along the chest wall is especially important. The position and size of any nodes should be recorded. The presence of lymphadenopathy should prompt referral to a breast specialist, though the significance of shotty nodes is unclear.

The character of breast lumps is particularly important. Characteristics that suggest cancer include a hard or gritty texture, immobility, an irregular border, and a size greater than 2 cm. A new "dominant" mass, or a gritty or growing lump, deserves evaluation by a breast specialist. Unfortunately, likelihood ratios for these signs indicating cancer are not very large, except for the presence of fixed lesions and lump size greater than 2 cm.⁹

After the history and physical examination, further assessment of breast lumps may include careful clinical follow-up, ultrasound, mammography, and/or biopsy. Guidelines for screening mammography will be reviewed in the National Guidelines section.

Mammography:

Mammography may be done as an adjunct to the physical examination in the evaluation of breast lumps or as a screening tool. Mammography is not generally useful in women under age 35 who present with a lump.¹⁰ Ultrasonography may be useful in the evaluation of lumps in these younger women, although it is important to refer to a breast specialist for any lesion in doubt.

Evaluating Symptoms
Mammography is usually recommended as part of the evaluation in women more than 35 years old who have a breast mass, to help evaluate the mass and to search for other lesions. It is an error to rely on negative mammogram results when there is a clinically suspicious lump. In such cases, the mammogram is a diagnostic adjunct to the surgeon, and it should not preclude referral if the findings are negative.

Mammographic findings that suggest cancer include increased density, irregular border, spiculation, and clustered irregular microcalcifications. Round, dense lesions on mammography may represent cystic fluid. Ultrasonography can often suggest a cystic lesion, and needle aspiration can confirm this.

Mammography findings are usually negative when mammography is used to evaluate breast pain, though it may be of reassurance value in this setting.

Screening
The age at which to begin mammography for screening is controversial. There have been 8 major trials of mammographic screening. The observed change in breast cancer mortality has varied widely among these studies. Differences in randomization techniques, quality of the mammograms, duration of follow-up, and evolving treatments for breast cancer during the trials have made it difficult to draw conclusions about mammographic screening. There have been several meta-analyses of the effect of mammographic screening. Differences in these derive from the time at which they were done, the presence or absence of follow-up data from individual trials, and the exclusion of certain trials in some meta-analyses.

A consensus has emerged that women between 50 and 69 should be screened by mammography. Results of a meta-analysis¹¹ of breast cancer screening trials found a 26% reduction in breast cancer mortality over 7 to 9 years among women screened at ages 50 to 74.

For women first screened in their 40s, the magnitude of breast cancer mortality reduction is at best 18% after 10 to 18 years of follow-up.¹² While some guidelines discuss starting mammographic screening earlier in women with a family history of breast cancer, data on the sensitivity of mammograms shows no better cancer detection rates in this group.¹³ However, due to a higher pre-test probability of breast cancer in those with a family history, the positive predictive value of mammograms is higher for those women (and therefore the false positive rate is lower for them).

The number needed to be screened to prevent a death from breast cancer has been estimated to be between 1,500 and 2,500 for women screened in their 40s.¹⁴ In addition, nearly one half of women screened starting at age 40 would have at least one abnormal screening mammogram during the subsequent 10-year period, leading to additional mammographic views and biopsies for a significant number. Many of these abnormal screening studies prove to be false positives.

If the patient or physician finds a palpable lump, diagnostic, or 4-view, mammography, with or without ultrasound, may be used to help guide diagnosis. Again, mammography is not sufficient to exclude cancer in the evaluation of a palpable mass (see discussion of ultrasonography and triple diagnosis).

Ultrasonography:

Ultrasonography does not have a role as a single or initial study in screening for breast cancer. However, it is very useful for evaluating breast lumps and in further defining mammographic abnormalities. It is especially useful in women younger than age 35; when a mass is noted on screening mammography but is not palpable; when a patient declines aspiration of a mass; and if a mass is too small or too deep for aspiration.

The risk of cancer is low if a simple cyst is found on ultrasound. One study found no cancers in 223 cysts.¹⁵ However, some experts recommend moving directly to fine-needle aspiration if a simple cyst is found at the site of a palpable mass.¹⁶ In our experience, we have found only one cancer in a "simple cyst" noted by ultrasound; the "cyst" was 2 cm in size, new, palpable by patient and physician, and warranted aspiration based on its size.

Fine-needle Aspiration
Fine-needle aspiration can be performed to aspirate a palpable suspected cyst. A 22- or 24-gauge needle is inserted into a cyst that has been stabilized with the other hand. If nonbloody fluid is obtained, it can be discarded, as no cancer was found in nonbloody cyst fluid in a large series.¹⁷ A clinical recheck should be performed in 4 to 6 weeks; recurrence of the lump should prompt surgical referral. Bloody fluid should be sent for pathologic analysis. Cancer is found in approximately 1% of bloody aspirates.¹⁷ When no fluid is obtained, cells can be obtained for cytologic evaluation with fine-needle aspiration biopsy.

Core Needle Biopsy:

A larger needle (14- to 18-gauge) is used for core needle biopsy. It is mostly used for evaluating nonpalpable breast masses (those found on MGM only), with ultrasound or mammographic guidance. Agreement between core needle biopsy and surgical biopsy was 94% in 7 studies.¹⁸

Triple Diagnosis:

The use of the physical examination, mammography, and fine-needle aspiration biopsy for diagnosing palpable lumps is referred to as "triple diagnosis." There is excellent sensitivity (99%) and specificity (99%) with this approach.¹⁹ If any of these three modalities suggests cancer, excisional biopsy is warranted.

THERAPY

Therapy for breast pain depends on accurate diagnosis. Antibiotics may be required for some infections; abscesses or hidradenitis may require surgical drainage. Breast reduction surgery may be helpful for those with pendulous breasts and resultant pain.

Treatment of fibrocystic disease is aimed at relieving pain. It may be helpful if the patient wears a soft brassiere with good support. Use of acetaminophen or a nonsteroidal anti-inflammatory drug may also help. Some patients note relief of pain with avoidance of caffeine, but this has not been proven effective by controlled studies. Use of vitamin E (400 units) is supported by some studies. Other maneuvers which may help include use of evening primrose oil (1500-3000 mg/day) or vitamin B6 (optimal doses are unclear, though it is prudent to avoid doses of vitamin B6 greater than 50 mg/day, due to risk of neuropathy). Oral contraceptives have shown some promise, and those containing progestins with androgenic properties (eg, 19-norprogestins) may be more beneficial. Danazol inhibits estrogen secretion and can be helpful; side effects include weight gain, acne, hirsutism, and amenorrhea.

Treatment of a breast lump or nipple discharge is dependent on the results of history, physical exam, and sometimes diagnostic studies. Characteristics of lumps suggesting malignancy include size (> 2 cm), firmness, immobility, and irregularity. The "triple diagnosis" protocol outlined in the previous section is helpful in sorting out whether lumps are benign or malignant. Benign lumps should be followed up clinically.

Nipple discharge can be caused by several factors. Some medications (eg, phenothiazines) can cause increased prolactin levels and thus nipple discharge; change in medication may be needed. Pituitary adenomas may lead to increased prolactin; endocrine studies, starting with a prolactin level, should be obtained if discharge is persistent; medical or surgical therapy may be warranted if a prolactinoma is identified. Nipple stimulation can sometimes cause discharge; cessation may be required to stop symptoms. Cytology of suspect nipple discharge (especially bloody discharge) can be obtained; galactography can also be performed. Fiberoptic ductography is available in some centers, and should improve our ability to find papillary lesions. If nipple discharge is associated with a palpable mass, referral to a breast surgeon is mandatory.

Once discovered—because of a palpable lump, nipple discharge, or screening—breast cancer is best treated by a multidisciplinary team, including surgeons and medical oncologist. Ongoing involvement of the primary physician is helpful for maintenance of emotional support and to monitor the overall health of the patient. A recent guideline for breast cancer treatment can be found on the Institute for Clinical Systems Improvement (ICSI) website.

OUTCOMES

It is estimated that there will have been 192,000 cases of breast cancer diagnosed in the United States in 2001. Breast cancer mortality has been decreasing since 1991 by about 1 percent per year, with an estimated 40,200 fatalities in 2001.²⁰ A similar decrease has been noted since the late 1980s in the United Kingdom. Breast cancer mortality has been decreasing even among women excluded from screening protocols by age, and there is evidence that adjuvant hormonal and cytotoxic treatment reduce mortality.²¹ ²² It is probable that the reduction in the past decade has been multifactorial, with screening, prompt evaluation of palpable lumps, chemotherapy, and hormonal therapy all contributing.²³

NATIONAL GUIDELINES

There are a number of breast cancer screening guidelines in North America. Each organization making recommendations has a publication or website with its guidelines. A comparison of the guidelines can be found at http://www.guidelines.gov.

The American Cancer Society recommends CBE every three years between ages 20-39. The National Cancer Institute recommends against screening MGM in women under 40, as there are no data showing benefit in this age group. The recommendation for a "baseline" mammogram has likewise disappeared from the American Cancer Society recommendations.

The American Cancer Society (ACS) and the American College of Radiology (ACR) recommend yearly screening with mammography and CBE starting at age 40 (although the ACR considers the value of CBE to be unproven). The Canadian Task Force recommends screening with CBE and mammography from age 50 to 69, and recommends against screening from age 40 to 49. The US Preventive Services Task Force (USPSTF) recommends screening with mammography with or without CBE every 1-2 years from age 40. They note that the age at which screening should be stopped is unclear, though women with comorbidity limiting life expectancy have less benefit. The NCI/NIH recommends screening with mammography with or without CBE from age 50 to 69. They present data on the apparent benefit of screening mammography starting at age 40, but note the smaller percentage of reduction in mortality than in women screened starting at age 50, and the longer follow-up needed to reach significant mortality reduction. They recommend against screening women under age 40, and note insufficient evidence for or against screening women over age 70 (Table 1).

As noted in the diagnosis section, it is estimated that the number of women needed to be screened with mammography to avoid one breast cancer death would be 1,500 to 2,500 for women screened in their 40s. Because of the high false-positive rate in this population, with a lower pretest probability of disease, about one half of women screened annually starting at age 40 would require a follow-up diagnostic mammogram during the subsequent 10-year period.

A Common-Sense Approach
In the absence of consensus in national guidelines, we favor the following approach to screening. In women younger than 40 who are concerned because of a family history of breast cancer, we review with them the data for apparent lack of efficacy of mammography.¹⁰ The sensitivity of mammograms is known to be less for young women, and to gradually rise with age.¹³ The relative contribution of the physical examination to diagnosis is probably greater in young women, so careful CBE on a yearly basis is probably useful. We also offer to calculate breast cancer diagnosis percent risk using the Gail model.⁸ If there is a family history of more than one first-degree relative with breast cancer, or a family history of bilateral premenopausal breast cancer, it is reasonable to discuss genetic testing.

For women in their 40s, we briefly review the data from clinical trials and the recommendations of the ACS and USPSTF. The public tends to be most familiar with the ACS guidelines. Many women want a straightforward recommendation. But if a woman seeks more information, we try to inform her about some of the subtle issues.

We offer mammograms to women who are age 40 or older, but we emphasize that, due to the lower sensitivity of mammography in younger women, in our opinion CBE is especially important.

The approach to women 50 to 69 years old is easier because of the consensus among guidelines. We recommend CBE and mammography annually. Of course, risk assessment may be important at any age. It is sometimes sought due to a new family history or a benign biopsy.

In women over age 70, although the incidence of breast cancer mortality is high, it represents a stable proportion of all deaths since other causes of mortality are also rising. Screening mammography trials that have included older women have not reported significant breast cancer mortality reduction in this group, though there are fewer women in this age range studied overall.

There have been attempts to identify women with the most to gain from continuing mammography. One suggestion is to target women with higher bone mineral density for biennial screening from 70 to 79, as case finding is more fruitful in this group.²⁴ Others have suggested that the overall health of the woman be assessed, and those with greater residual life expectancy be targeted for screening. The latter is the basic approach we take. If the woman in good health, we continue to offer CBE and MGM.

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REFERENCES

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Revised June 8, 2004

Pelin Batur, MD

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Definition

Prevalence

Pathophysiology

Signs and
Symptoms

Diagnosis

Therapy

Outcomes

References

National Guidelines

Institute for Clinical Systems Improvement