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From the Townsend Letter
February/March 2014

Environmental Medicine Update
Breast Lumps: Clinical Pearls and Perils
by Marianne Marchese, ND
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Breast problems are a major reason why women visit their primary care physicians. Breast diseases in women constitute a spectrum of benign and malignant disorders. The most common breast problems for which women consult a physician are breast pain, nipple discharge, and a palpable mass. When a woman finds a breast lump, it often causes worry and distress even though most are benign. Proper evaluation and workup of a breast mass are key to diagnosis and treatment

Breast Lumps
Normal glandular tissue of the breast is nodular. This is a general pattern or consistency of the breast that includes persistent lumpiness which is generally not abnormal when it is related to the menstrual cycle. Dominant masses are characterized by persistence throughout the menstrual cycle.

Common tumors and masses include:

  • cysts
  • nodularity or glandular
  • fibroadenoma
  • galactoceles
  • duct ectasia
  • phyllodes tumor
  • fat necrosis
  • intraductal papilloma
  • sclerosing adenosis
  • lipoma
  • hamaratoma
  • diabetic mastopathy
  • breast cancer

A cystic breast mass a common cause of dominant breast lumps. It may occur at any age but is uncommon in postmenopausal women, fluctuates with menstrual cycle, and is well demarcated from the surrounding tissue. It is characteristically firm and mobile and may be tender and difficult to differentiate from solid mass. Fibrocystic breast disease is the most common of all benign breast disease and is seen in women between ages 20 and 50. 50% of women with fibrocystic changes have clinical symptoms and 53% have histologic changes. Women may present with bilateral cyclic pain, breast swelling, palpable mass, and heaviness.1 Fibroadenoma is the second most common benign breast lesion. It usually presents as a well-defined mobile mass, is commonly found in women between ages 15 and 35 years, and is thought to be due to hormonal influence. Fibroadenomas may increase in size during pregnancy or with estrogen therapy. They can range from 5 cm to 20 cm in diameter.2,3 Complex fibroadenomas contain other proliferative changes such as sclerosing adenosis, duct epithelial hyperplasia, and epithelial calcification and are associated with slightly increased risk of cancer.2,3 A galactocele is a milk-filled cyst from overdistension of a lactiferous duct. They presents as a firm, nontender mass in the breast, commonly in upper quadrants beyond areola.

Pearl: Diagnostic aspiration of a galactocele is often curative.

Duct ectasia is generally found in older women. Dilatation of the subareolar ducts can occur. A palpable retroareolar mass, nipple discharge, or retraction can be present. Phyllodes tumors are rare, mostly benign tumors that grow rapidly. 1 in 4 is malignant; 1 in 10 metastasizes. They create bulky tumors that distort the breast and may ulcerate through the skin due to pressure necrosis. The tumor has a smooth, sharply demarcated texture and typically is freely movable. It is a relatively large tumor, with an average size of 5 cm. However, lesions of more than 30 cm have been reported.4 Fat necrosis is rare and secondary to injury or trauma. It can form after biopsy or surgery of the breast. It is a tender, ill-defined mass and occasionally presents with skin retraction. Intraductal papilloma is a benign growth within the ductal system and presents as bloody nipple discharge.1

Pearl: Excision is the only way to differentiate intraductal papilloma from carcinoma.

Sclerosing adenosis is a benign condition of the breast in which extra tissue develops within the breast lobules. This is sometimes placed under the category of borderline breast disease. Many women with sclerosing adenosis experience recurring pain that tends to be linked to the menstrual cycle. Clinically it is not palpable in 80% of the cases, while in some cases, it might cause skin retraction.5 A breast lipoma is a benign breast lesion composed of fat cells. Patients may present with a painless palpable breast lump that is soft and mobile. Fine needle biopsy of these lesions reveals fat cells with or without normal epithelial cells.
Pearl: Mammography and ultrasound scanning of a lipoma are usually negative, unless it is large.

Hamartoma of the breast is an uncommon benign tumorlike nodule, also known as fibroadenolipoma, lipofibroadenoma, or adenolipoma. It is composed of varying amounts of glandular, adipose, and fibrous tissue. Clinically, hamartoma presents as a discrete, encapsulated, painless mass. While it can present as a painless soft lump, it may also present as unilateral breast enlargement without a palpable lump. This lesion can be very easily underestimated if the clinical finding of a distinct lump or breast asymmetry and the imaging features are not interpreted thoroughly.6 Diabetic mastopathy is noncancerous lesions in the breast most commonly diagnosed in premenopausal women with type 1 diabetes. Symptoms may include hard, irregular, easily movable, discrete, painless breast mass(es).7 The prevalence of diabetic mastopathy has been found to be <1% of benign breast diseases, but prevalence can range from 0.6% to 13% in type 1 diabetics.
Peril: Diabetic mastopathy is infrequently encountered since breast examination is not performed routinely in younger diabetic patients.

Physical examination
A complete clinical breast examination (CBE) includes an assessment of breasts and the chest, axillae, and regional lymphatics. In premenopausal women, the CBE is best done the week following menses, when breast tissue is least engorged. With the patient in an upright position, the physician visually inspects the breasts, noting asymmetry, obvious masses, and skin changes, such as dimpling, inflammation, rashes, and unilateral nipple retraction or inversion. Next, the physician thoroughly palpates breast tissue in supine with one arm raised. Nipple discharge is not elicited on CBE, as abnormal worrisome nipple discharge is typically spontaneous and unilateral. CBE sensitivity can be improved by longer duration (i.e., 5 to 10 minutes) and increased precision (i.e., using a systematic pattern, varying palpation pressure, and using three finger pads and circular motions). CBE can detect up to 44% of cancers, up to 29% of which would not have been detected by mammography.8 A palpable breast mass is considered dominant if there is a 3-dimensional lesion distinct from the surrounding tissues and asymmetric relative to the other breast.9
Pearl: Abnormalities detected on physical examination in women over 40 should be regarded as possible cancers until they are documented to be benign.10

Standard Workup
Mammography is the standard for the evaluation of breast lumps, yet 10% to 30% of breast cancers may be missed at mammography. Possible causes for missed breast cancers include dense parenchyma obscuring a lesion, poor positioning or technique, perception error, incorrect interpretation of a suspect finding, subtle features of malignancy, and slow growth of a lesion. Steps to improve accuracy of mammography include performing diagnostic instead of screening mammography, reviewing clinical data, and using ultrasound to help assess a palpable mass.11
Ultrasonography is recommended in women under 35 years old, and both ultrasonography and mammography are recommended in those 35 years old or above. Women with dense breast tissue will require mammogram with ultrasound.12 Often breast magnetic resonance imaging (MRI) is used as an additional diagnostic tool, either when other imaging is negative and there is a palpable mass, or to differentiate size of mass found on other imaging. Screening MRI is recommended for women with an approximately 20% to 25% or greater lifetime risk of breast cancer, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin's disease.13 Screening with both MRI and mammography might rule out cancerous lesions better than mammography alone in women who are known or likely to have an inherited predisposition to breast cancer. No matter what method of imaging is utilized, a palpable breast lump confirmed with imaging will be biopsied for diagnosis and to rule out breast cancer.
Pearl: For a palpable mass on CBE, order a diagnostic mammogram with ultrasound.
Peril: Mammogram alone is not adequate for women with dense parenchyma.

Nonstandard Workup
Some women refuse standard imaging in the workup of breast lumps due to fears of radiation exposure associated with mammography and various other reasons. They often ask if alternative testing methods exist that might help determine if a breast mass is benign or malignant. Testing for cadherins might be one of those methods. Cadherins are cell–cell adhesion glycoproteins that play an essential role in development and maintenance of adult tissues and organs. The expression of P-cadherin is restricted only to basal or lower layers of epithelia, including prostate and skin and also to breast myoepithelial cells (MECs).14 Normal breast ducts and lobules comprise two epithelial layers. Loss of the outer MEC layer is hallmark of infiltrating carcinomas of the breast. MEC layer is retained in most benign breast masses. A recent study looked to evaluate the expression of P-cadherin as MEC marker in the differential diagnosis of benign and malignant breast lesions. Immunohistochemical staining was done using P-cadherin-specific antibody on formalin fixed paraffin-embedded sections of 25 benign and 15 malignant breast lumps. All 25 cases of benign breast lesions showed positive P-cadherin immunostaining, while only 4 out of 15 cases of infiltrating ductal carcinoma showed positive immunostaining for P-cadherin. P-cadherin immunoreactivity was seen in 100% of benign cases, whereas only 27% of malignant cases were P-cadherin immunoreactive.14 This may be a useful marker in the differential diagnosis of breast lesions wherever there is confusion in diagnosis with routine methods.
Breast thermography is a noninvasive and nonionizing medical imaging. Thermography produces an infrared image that shows the patterns of heat and blood flow on or near the surface of the body. It is temperature dependent. Cancerous and precancerous tissues have a higher metabolic rate, resulting in growth of new blood vessels supplying nutrients to the fast-growing cancer cells. As a consequence, the temperature of the area surrounding the precancerous and cancerous breast tissue is higher when compared with the normal breast tissue temperature. Thermogram may be useful as an additional screening tool to determine whether a breast lump is benign or cancerous but not in differentiating various benign breast masses. As a screening for breast cancer, it is controversial. A recent study compared thermogram with mammogram and found sensitivity for thermography as a screening tool was 25% (specificity 74%) compared with mammography. Sensitivity for thermography as a diagnostic tool ranged from 25% (specificity 85%) to 97% (specificity 12%) compared with histology.15
The HALO Mamo Cito Test is a relatively new method of determining whether a breast mass is benign or cancerous. It is hailed as the equivalent to a cervical Pap smear test. Nipple fluid aspirate is collected and sent for cytology in order to evaluate the cellularity for the diagnosis of breast cancer. Several studies support its use in breast cancer detection and several studies cite its inaccuracy.16,17
Blood tests are another nonstandard method of evaluation. The dtectDx Breast test looks at blood-based biomarkers that are highly associated with early breast cancer development. It is not a genetic test for breast cancer. It analyzes serum concentrations of five protein biomarkers – interleukin-8 (IL-8), IL-12, vascular endothelial growth factor, carcinoembryonic antigen, and hepatocyte growth factor – via enzyme-linked immunosorbent assay to detect breast cancer. A study in the Journal of Clinical Oncology has demonstrated positive outcomes using dtectDx Breast.18 This test is currently undergoing further clinical trials to establish an acceptable algorithm for generation of a single numerical score from the combination of the 5 cancer biomarkers that comprise the dtectDx Breast assay, and to define a numerical score cutoff that differentiates malignant from nonmalignant breast cancer in this population of women.
Peril: Nonstandard breast evaluation methods should not be used in place of standard diagnostic tests, but in addition.

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