What is the most likely diagnosis of this breast lesion?A 32-year-old woman presents for evaluation of a lump that she noticed in her right breast on self-examination. She says that she does not examine herself often, but that she thinks that this lump is new. She has not had any nipple discharge and has no breast pain, although the lump is mildly tender on palpation. She has never noticed any masses before and has never had a mammogram. She has no history of breast diseases and has never had a biopsy. There is no history of breast cancer in the family. She takes oral contraceptive pills regularly, but no other medications. She does not smoke cigarettes or drink alcohol. She has never been pregnant. On examination, she is a well-appearing, but somewhat anxious, thin woman. Her vital signs are within normal limits. Her general physical examination is normal. Examination of her breasts reveals no skin dimpling or retraction and no nipple discharge. In the lower outer quadrant of the right breast there is a 2-cm, firm, well-circumscribed, movable mass that is mildly tender. No other masses are felt, but the breast tissue is noted to be firm and glandular throughout. No axillary, supraclavicular, or cervical lymphadenopathy is appreciated.
What is the most likely diagnosis of this breast lesion?
What is the next step in evaluation?
What is the recommended follow-up for this patient?
Summary: A 32-year-old woman presents for evaluation of a lump in her right breast that she found on breast self-examination (BSE). The lump is found to be 2 cm in size, firm, and mobile. No adenopathy is noted.
• Most likely diagnosis: Breast cyst.
• Next step in evaluation: Needle aspiration of cyst.
• Follow-up: If aspiration of the cyst results in complete resolution of the mass, and if the fluid is clear/yellow, follow-up clinical examination in 1 to 2 months to ensure no recurrence; if aspiration does not make the mass disappear, if the fluid is bloody, or if the lesion recurs, further evaluation with biopsy of the lesion is indicated.
1. Learn how to workup a breast mass.
2. Know the risk factors for breast cancer.
3. Know how to manage benign breast diseases.
A palpable breast mass is a potentially frightening finding for a woman. The media has widely disseminated the statistic that 1 in 8 women will have breast cancer in their lifetime. Consequently, the evaluation of the breast mass is designed to answer the one question that is on the patient’s mind, whether she says it or not: Is this lump breast cancer? Fortunately, most palpable breast masses are not cancerous. Unfortunately, a definitive determination of whether a lesion is benign or malignant cannot be made by history and physical examination findings only.
Certain factors have been identified as increasing a woman’s risk of breast cancer:
• A family history of breast cancer in a first-degree relative (parent, sibling), especially if the cancer occurred in a premenopausal woman and was bilateral, is associated with an increased risk. This risk factor could indicate deleterious BRCA-1/BRCA-2 genes.
• Early age at menarche (<12 years), late age of menopause (>55 years), and nulliparity or first live birth after the age of 30 years are also associated with higher risks.
• The use of hormones, either estrogen alone or combined with progesterone, are considered to confer higher risks, although recent studies question whether oral contraceptives pose any significant risk.
• Lifestyle considerations, including obesity, physical inactivity, and alcohol use (>3 drinks per day), also are identified risk factors.
• History of previous breast disease, especially biopsies showing atypical hyper-plasia, carcinoma in situ, or prior breast cancer, are associated with increased risks.
In the case presented, there are several pieces of information presented that lead toward a likelihood of a benign process. Breast cancer can occur at any age, but approximately 70% of breast cancers occur in women older than age 50 years. You can never overlook the possibility of malignancy in a woman who is in her thirties, but the possibility of cancer is lower in her than in an older woman. The characteristics of the lesion are also more consistent with a benign, probably cystic, process. It is described as well-circumscribed, firm, mobile, tender, and with no overlying skin changes. Lesions that are hard, fixed in place, nontender, have indistinct borders, or have overlying skin dimpling/retraction are more suggestive of cancer. Nevertheless, no individual characteristic on examination is diagnostic and an appropriate evaluation is necessary.
ACROMEGALY: A condition that results from the excessive production of growth hormone by a pituitary adenoma. Among the numerous physical effects of the excessive growth hormone, menstrual irregularities and breast discharge may result.
DUCT ECTASIA: Inflammation of a mammary duct below the nipple, which can lead to duct obstruction, a tender mass, and duct discharge.
INTRADUCTAL PAPILLOMA: A benign tumor growth into a mammary duct, often with a resultant palpable small mass and duct discharge.
Following a complete history, with an emphasis on factors that may confer an increased risk of cancer, a careful examination of both breasts should be performed. The breast examination should include a visual inspection for skin changes, dimpling, retraction, and asymmetry, and should note the presence and quality of any nipple discharge (color, presence of blood, etc).
Examination by palpation should be performed in a systematic manner to include all quadrants of the breast, as well as the superficial, intermediate, and deep breast tissue. Specific characteristics of any palpable lumps, including size, location, tenderness, mobility, firmness, and distinction of the mass from the surrounding tissue, should be noted, both to assist in developing a diagnosis and to allow for serial examinations to determine if the mass is changing. The breast examination should also include palpation of the axilla and supraclavicular regions to identify the presence of enlarged lymph nodes. The characteristics of the mass and the age of the women will provide initial clue into likely diagnosis (Table 49–1).
Table 49–1 • TYPICAL CHARACTERISTICS OF BREAST LUMPS ON PHYSICAL EXAMINATION
The identification of a new breast solid mass particularly in women older than 35 years should prompt triple assessment, which includes a clinical breast examination, imaging (mammography), and pathology assessment either by core biopsy or surgical excision. Very few breast cancers are missed using the triple test.
For women younger than 35 years of age, suspected lesions characteristic of fibroadenoma or fibrocystic changes can be assessed by ultrasonography, rarely mammography followed by fine-needle aspiration with histologic evaluation. Ultra-sonography can be used as an adjunct to mammography in an effort to determine if the lesion is solid or fluid filled. It can also be used in women with denser breasts or women with persistent breast pain without evidence of mass by mammography. For pregnant females with a new breast complaint, targeted ultrasonography is the first-line imaging choice.
Fine-needle aspiration (FNA) can be both diagnostic and therapeutic and is performed if the mass is cystic and symptomatic. A FNA that identifies fluid that is clear, yellow, or green-tinged and that results in complete resolution of a mass is diagnostic of a benign cyst. In this setting, the fluid can be discarded and no further workup is necessary. The patient should be seen in follow-up in 4 to 6 weeks for reexamination to evaluate for recurrence of the lesion.
If the mass does not completely resolve, if the fluid withdrawn is bloody, if no fluid is aspirated, or if the lesion is found to recur on follow-up or has complex nature (containing cystic and solid components), then further evaluation is indicated by stereotactic core-needle or excisional biopsy. Several biopsy techniques are used in practice. FNA can be performed on solid lesions; however, it should be used for lesions most likely to be cystic. It is the least invasive and simplest procedure, but also has the highest risk of false-negative or nondiagnostic results. Core-needle biopsy and mammotome biopsy use larger cutting needles to obtain larger tissue samples. These are usually performed using ultrasound or mammographic guidance by a radiologist or surgeon. These procedures have a higher chance of providing a diagnostic sample but are more invasive and costlier than FNA. Although surgical excision is the most invasive and expensive diagnostic method, it is indicated if stereotactic biopsies show atypical ductal hyperplasia and is also therapeutic by removing the lesion in question.
Breast pain (mastalgia) is the most frequent breast-related complaint for which women present for evaluation. The etiology of chronic mastalgia is often unknown. As with the presentation of a breast lump, the patient’s primary fear, whether spoken or unspoken, is whether the pain is a manifestation of breast cancer. As such, the evaluation should include a history to evaluate for high breast cancer risk status, a careful breast examination, and a screening mammography in women for whom it is routinely indicated. Any abnormalities found in the primary evaluation should be worked up as appropriate. Breast pain is not a common presentation of breast cancer, particularly when it is bilateral breast pain.
Most breast pain may be categorized as cyclic mastalgia, noncyclic mastalgia, or extramammary pain. Cyclic mastalgia is usually diffuse, bilateral often radiating to axilla and arm and related to the woman’s menstrual cycle. Pain occurs during late luteal phase and resolves with onset of menses. In some cases, it can be unilateral. Noncyclic mastalgia may be continuous or intermittent, but is not associated with the menstrual cycle. It is more commonly unilateral and more prevalent in postmenopausal women. Extra-mammary pain is breast pain secondary to another etiology. This is often chest wall pain, but sometimes, the underlying cause may be difficult to determine.
Etiology of most mastalgia is unknown. Common causes of mastalgia are:
• Pregnancy
• Mastitis
• Thrombophlebitis
• Cyst
• Benign tumors
• Cancer
• Musculoskeletal cause
• Stretching of Cooper ligaments
• Pressure from brassiere
• Fat necrosis from trauma
• Hidradenitis suppurativa
• Medications such as oral contraceptive pills (OCPs), antidepressants, antipsychotics, antihypertensive, and others
Laboratory testing is usually unnecessary in the evaluation of mastalgia, although a pregnancy test should be performed in reproductive-age women. Hormonal contraceptives or hormone replacement therapy may be causes of breast pain and consideration should be given to discontinuation or reduction of estrogen dosages. An appropriately fitted supportive bra and lifestyle changes, such as tobacco cessation and stress reduction techniques, are often successful in alleviating symptoms. Evening primrose oil, caffeine reduction, and vitamins have not been shown to provide much relief. Topical NSAIDs have shown the most promise. Other low-risk treatments with possible efficacy include soy protein, low-fat high-carbohydrate diet, and chasteberry extract. For women with unrelenting pain in spite of the above modifications, danazol, an antigonadotropin, is Food and Drug Administration (FDA) approved for the treatment of breast pain, but is relatively expensive and has numerous side effects (hair loss, acne, weight gain, and irregular menses). Other options include tamoxifen, toremiphene, and bromocriptine, which are hormonal therapies with significant risks that have some evidence for efficacy in refractory cases.
Nipple discharge is usually caused by a benign process. Up to 25% of women will have this symptom during their life. Nipple discharge that occurs only with nipple stimulation, that is clear, yellow, or green, and that appears from multiple ducts is usually physiologic. This discharge often goes away if efforts are made to reduce nipple stimulation (including ceasing efforts to check to see if the discharge will still occur).
Discharge that is spontaneous, persistent, bloody, from a single duct, associated with a mass, and occurs in women over 40 years of age is more likely to represent a pathologic process. In this setting, the most common causes are intraductal papillomas, duct ectasia, cancers, and infections. If the discharge is not obviously bloody, a fecal occult blood test card can be used to test for occult blood.
Following the initial history and physical examination, mammography should be performed in all women with a spontaneous or bloody discharge and in any woman in whom routine mammographic evaluation is indicated. Palpable breast masses should be appropriately evaluated. The treatment of most unilateral, spontaneous, or bloody nipple discharges is surgical excision of the terminal duct involved. This both resolves the problem and allows for pathologic diagnosis of the problem.
Galactorrhea is a discharge of milk or a milk-like secretion from the breast in the absence of parturition or beyond 6 months postpartum in a non–breast-feeding woman. The secretion may be a milky or serous (yellow) appearing, intermittent or persistent, scant or abundant, free-flowing or expressible, and unilateral or bilateral. If the clinician is unsure if the discharge is galactorrhea, the discharge can be sent off for staining and microscopic analysis. Galactorrhea will contain few cells and will have fat globules. The condition is more common in women who are 20 to 35 years of age and in previously pregnant women.
Galactorrhea is associated with stress, physical irritation, numerous medications, hypothyroidism, chronic renal failure, hypothalamic-pituitary disorders, hormone-secreting neoplasms (most commonly pituitary adenomas), or may be idiopathic, but is not associated with breast cancer.
Numerous pharmacologic agents are causes of galactorrhea. These agents can block dopamine and histamine receptors, deplete dopamine stores, inhibit dopamine release, and stimulate lactotrophs. Common medications and classes of medications associated with galactorrhea include: serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), atenolol, verapamil, antipsychotics, H2 histamine blockers (cimetidine), and opiates, to name a few. Estrogen in oral contraceptives can cause galactorrhea by suppressing the hypothalamic secretion of prolactin inhibitory factor and by direct stimulation of the pituitary lactotrophs.
Offending medications should be discontinued, if possible. Prolactin and thyroid-stimulating hormone levels should be drawn to evaluate for endocrine abnormalities. Assessing electrolytes and renal function can assess for renal failure, Cushing disease, and acromegaly. Imaging of the pituitary to evaluate for a pituitary adenoma with magnetic resonance imaging (MRI) is indicated if the prolactin level is significantly elevated.
Treatment is geared at addressing the underlying condition, that is, hypothyroidism should be treated with hormone replacement. It is also geared toward severity of the prolactin level and pending fertility status.
Dopamine agonists are the treatment of choice in most patients with hyperprolactinemic disorders. Bromocriptine is the preferred agent for treatment of hyper-prolactin-induced anovulatory infertility. Surgical resection rarely is required for prolactinomas.
49.1 A 34-year-old woman notes that she has had breast nipple discharge for 2 months. A urine pregnancy test is negative. She was on antipsychotic medication for a history of schizophrenia, but has not taken the medication in 6 months. Laboratory studies reveal normal thyroid-stimulating hormone (TSH), T3, and T4 and the thyroid is not palpable. The physician makes an assessment that the circumstances and characteristics are likely associated with a pathologic process. Which of the following characteristics is most concerning?
A. Yellow
B. Bilateral
C. Bloody
D. Present with nipple stimulation
49.2 A 52-year-old woman has a palpable breast lump. An attempt at FNA does not result in aspiration of fluid. A mammogram is read as normal. Her mother was diagnosed with breast cancer at age 45. She does not smoke but socially drinks alcohol. She currently uses low-dose estrogen contraception pills and takes 1200 mg of calcium daily. She began her menstrual periods at age 10 and she had her first child at age 24. Which of the following is the appropriate next step?
A. Repeat clinical examination in 4 to 6 weeks.
B. Repeat mammogram routinely in 1 year.
C. Referral for biopsy.
D. Discontinuation of her hormone replacement therapy.
49.3 A 29-year-old woman comes into the clinic with complaints of left-sided nipple discharge. On further questioning she states that the discharge is milky in color. She is a G2P2 with the last birth 3½ years ago. She breast-fed both children for 9 months. She is on no medications and is having regular menstrual periods. You express a small amount of nonbloody milky discharge from several ducts from the left nipple and are unable to express discharge from the right. Which of the following is the best diagnostic step?
A. Send for diagnostic mammogram. If negative, reassure that the discharge is not significant.
B. Refer to a breast specialist for evaluation for unilateral nipple discharge.
C. Obtain TSH, free T4, and prolactin levels.
D. Obtain levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin-releasing hormone (GnRH).
49.1 C. Nipple discharges that are spontaneous, unilateral, persistent, bloody, and associated with a mass are more likely to represent pathologic processes. Most of these are still benign (eg, papilloma, duct ectasia), but evaluation and surgical intervention are usually required.
49.2 C. A biopsy is the next appropriate step in this setting. A negative mammogram is not diagnostic of a benign process and does not rule out the possibility of having a breast cancer. A tissue diagnosis is needed in this setting especially with a known first-degree relative with breast cancer and early age of menarche.
49.3 C. The evaluation and management of most cases of galactorrhea can be handled by the primary care physician. If pituitary adenoma is diagnosed then the patient can be referred for specialty care. Milky discharge, galactor-rhea, from multiple ducts in the nonlactating breast may occur in certain syndromes—it is usually due to an increased secretion of pituitary prolactin. A pregnancy test should be the first evaluation. Hypothyroidism can also cause hyperprolactinemia. Psychiatric agents such as chlorpromazine- and estrogen-containing agents such as the oral contraceptive pills may also cause milky discharge.
Approximately 1% of breast cancer occurs in men. A new palpable mass in a man’s breast should prompt a diagnostic evaluation.
Remember that the question in the mind of just about every woman presenting with a breast-related complaint is, “Do I have breast cancer?” The job of the physician is to both manage the presenting complaint and to answer this question.
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