Fibrocystic change in the breast is an all-encompassing term used to describe many different breast changes. Examples of benign lesions that are generally considered when fibrocystic changes are discussed are multiple lesions of fibrous disease, intraductal papilloma, cysts, and solid masses such as fibroadenoma (Table 17-1). These changes affect almost all women at some time in their lives. Frequently pain is present, which calls attention to the problem. Pain, fluctuations in size, and multiple lesions are common features that help differentiate these generally benign lesions from cancer.

Nipple discharge is more commonly associated with benign lesions than with cancer. A postmenopausal woman who has some duct ectasia or who has borne children can manually produce nipple discharge. The most common cause of serous or serosanguineous nipple discharge is a benign intraductal papilloma, along with medications such as tricyclines and antidepressants. Discharge is usually significant only if it is spontaneous and persistent. The discharge may be clear or bloody (Townsend et al, 2012). Chronic unilateral nipple discharge, especially if bloody, should prompt an investigation for occult carcinoma.

Breast cancer in men is rare; less than 1% of breast carcinomas arise in men. The average age at diagnosis is approximately 68 years. Risk factors include increased age, radiation exposure, estrogen treatment, Klinefelter syndrome, heavy alcohol intake, obesity, female relatives with a breast cancer diagnosis, and families in which breast cancer susceptibility gene 2 (BRCA2) mutation has been identified (Ohio State University Medical Center, 2013). The most common type of tumor is infiltrating ductal carcinoma. Paget disease of the nipple, inflammatory carcinoma, and intraductal cancer have also been reported in men. Symptoms include breast lumps, nipple inversion, nipple discharge, pain or pulling feelings and skin or nipple changes such as dimpling, puckering, redness, or scaling. Staging of male breast cancer is identical to staging for female breast cancer. Treatment may include surgery, radiation therapy, chemotherapy, and hormone therapy. Before hormone therapy begins, a hormone receptor test is done to determine if estrogen and progesterone receptors are present. Adjuvant therapy of radiation, chemotherapy, or hormone treatment can be given after to destroy cancer cells that cannot be detected. According to a large study of male breast cancer, male patients have more advanced disease at diagnosis, lower 5-year survival rates, and shorter median overall survival rate than women (Healthday, 2013).

Breast cancer affects primarily women. Until it can be prevented, early detection is the best hope for cure. It has, in the past, been recommended that all women should practice monthly self-examination to detect palpable lesions, and they should immediately report any changes or masses to a physician. However, the efficacy of breast self-examination (BSE) in decreasing cancer mortality is being questioned. Allen and colleagues (2010) suggest patients with breast cancer risk factors such as gene mutation, family history, obstetric and gynecologic history, demographics, and environmental risk factors should be taught BSE. The U.S. Preventive Services Task Force (USPSTF) does not recommend BSE (Centers for Disease Control and Prevention [CDC], 2012). The most common form of breast cancer at present is infiltrating ductal carcinoma (Table 17-2).

The cause of breast cancer remains unknown. Many factors, including environmental, dietary (National Cancer Institute [NCI], 2011), and familial influences have been suggested as contributors to its development (Table 17-3). The belief that breast cancer spreads by direct extension from its initial site in the breast to adjacent lymph nodes may not always be correct. Breast cancer may be a systemic condition at the time of diagnosis. Distant metastases may have already occurred without adjacent lymph node involvement at the time of palpable detection. This could explain why radical breast surgery of the past, which involved removal of the affected breast and all axillary and thoracic lymph nodes, did not greatly lower mortality. Survival from breast cancer is best when detected early, reducing axillary lymph node involvement and improving long-term survival. Tumor size can usually be correlated with involvement of lymph nodes. The larger a tumor is, the more likely it is that lymph nodes are involved.

Clinical use of accelerated partial breast irradiation (APBI) is a current treatment. In APBI the radiation is focused on the area of greatest risk for tumor recurrence, the lumpectomy site, instead of whole breast irradiation (WBI). Such focused radiation treatment therapies reduce the traditional 6-week radiation treatment plan to 1 week to 3 weeks (ACS, 2012). Although external beam radiation therapy of the whole breast after lumpectomy has been the standard of care for treating early stage breast cancer, APBI is being used increasingly as an alternative treatment option for carefully selected patients.

Brachytherapy, also known as internal radiation, is another delivery method of radiation. Radioactive seeds are placed precisely into the adjoining cancerous breast tissue. There are two kinds of brachytherapy: interstitial and intracavitary. In interstitial brachytherapy, many small, hollow catheters are inserted into the breast around the lumpectomy area and are left in place for several days. Radioactive pellets are inserted into the catheters for short periods each day and then removed. It is not as common today as intracavitary brachytherapy, which is a form of APBI that involves placing a source of radiation into the lumpectomy site for a short period and removing it. It is usually administered twice a day for 5 days on an outpatient basis (ACS, 2012). Clinicians are likely to prefer the newer intracavitary brachytherapy technique for APBI because this method is less invasive and less technically demanding than interstitial techniques.

Minimally invasive cryoablation technology to freeze and destroy solid breast tumors is another option for treatment of a breast tumor. Another breast surgery alternative is focused ultrasound (FUS) with magnetic resonance guidance (MRgFUS), which allows for imaging and tissue temperature monitoring while controlling the FUS beam direction during ablation of breast lesions (Tempany et al, 2011).

Imaging methodologies, such as mammography and ultrasonography (US), have helped detect breast masses too small for clinical detection. A recent study supports the need to identify and track breast cancer screening disparities in the United States (Research Highlight). The American Cancer Society (ACS) recommends clinical breast exams by a physician every 3 years for women ages 20 to 39 years, with annual clinical breast exams and mammograms for women 40 and older (Table 17-4). Women who are at high risk should have magnetic resonance imaging (MRI) and a mammogram every year. High-risk women include those who have a known breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) mutation, those who have a first-degree relative with a BRCA1 or BRCA2 gene mutation, and those who have a history of breast cancer, ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), atypical ductal hyperplasia, or atypical lobular hyperplasia (ACS, 2012). The USPSTF advises women ages 50 years and older to have a screening mammogram every 2 years (CDC, 2012). Many professional organizations such as the American Medical Association, American College of Surgeons, American College of Obstetricians and Gynecologists, and the American College of Radiology advocate mammography to begin at age 40.

The most common screening mechanism for asymptomatic women is mammography (Figure 17-5). In mammography the entire breast is visualized as x-ray beams are directed in several planes through it. Mammograms detect abnormal-appearing densities, irregular or spiculated margins, microcalcifications, and clusters of calcium deposits that are clinically nonpalpable. Screening mammography is the most helpful in early detection because it can discover cancer several years before physical symptoms such as a lump develop. Often previous mammograms are used for comparison. The accuracy of mammography depends on careful x-ray technique and breast size, structure, and density. Radiation dosage varies with individuals and techniques. As a result of improved radiologic techniques, radiation exposure in a mammogram is very low. The benefits of this screening mechanism far outweigh the minute risks of radiation exposure. Advances in computer-assisted detection allow the computer to analyze the mammogram, placing asterisks and triangles on small potential problem areas, which a radiologist then reviews. In some instances, such as when a lesion previously detected in a mammogram is too small to palpate, mammograms are repeated immediately before surgery. The lesion is localized by the insertion of a needle or a wire within a needle (often referred to as “needle” or “wire” localization) (Figure 17-6). If screening mammography reveals a suspicious area, the patient is asked to return for diagnostic mammography.

Digital mammography, also known as full-field digital mammogram (FDDM), is similar to a standard mammogram in that an x-ray is used to take images of the breast. The mammograms are recorded and viewed on a computer where the image size, brightness, or contrast in certain areas of the film can be adjusted and seen more plainly. Digital images can be sent electronically to other sites for viewing and consulting with breast specialists. Radiologists also can use software to interpret digital mammograms. Digital screening mammograms are more accurate than film screening mammograms, with a 70% detection rate compared with 55% for film screens. Women most likely to benefit from digital screening are those younger than 50 with dense breast tissue and who are premenopausal or perimenopausal (ACS, 2012). When a palpable mass or other abnormality is identified on screening mammography, additional diagnostic mammographic views are obtained, and the radiologist assigns a Breast Imaging Reporting and Data System (BI-RADS) score (Box 17-1). US may then be ordered.

US differentiates between solid and cystic lesions. A cyst is a fluid-filled sac and is considered a benign finding. A solid mass may suggest malignancy and requires further evaluation. As a screening methodology alone, its sensitivity and specificity are less definitive than mammography. US can be useful with dense or dysplastic breasts and in pregnant or lactating women. Women 30 to 39 years of age benefit most from US, which has a sensitivity of 95.7% compared with 60.9% for mammography and discovers more cancerous lesions than mammography (Lehman et al, 2012).

MRI is used as an adjunct to mammography in the detection of breast lesions. MRI uses a strong magnet to produce a complete image of the breast. There is no radiation. Breast MRI can image dense breast tissue, which shows poorly with conventional mammography. The ACS recommends that MRI be used for women at high risk. Such women include those who have known breast cancer–associated BRCA1 or BRCA2 gene mutations, have a first-degree relative with a BRCA1 or BRCA2 gene mutation, have a lifetime risk of breast cancer of 20% to 25% or greater according to risk assessment tools, and had radiation therapy to the chest between 10 and 30 years of age. MRI also better determines definite size of the cancer and is useful in women with breast augmentation.

Molecular breast imaging (MBI) refers to a number of modalities that use a radiopharmaceutical agent in scanning, including breast-specific gamma imaging (BSGI) and positron emission mammography (PEM). It involves injection of a short-lived radiotracer, which is absorbed by breast tissue and preferentially so by breast tumors. MBI is especially useful in detecting breast cancer in women with dense breasts, those who present with a palpable abnormality not found on mammogram or US, and those who cannot tolerate MRI or who have metallic implants (Kaplan, 2011).

Deoxyribonucleic acid (DNA)–based genetic testing for BRCA1 and BRCA2 is recommended for women with family histories that suggest risk for these gene mutations. These mutations lead to the development of hereditary breast and/or ovarian cancer in affected women. Individuals with a harmful BRCA mutation have a lifelong chance of up to 80% risk of developing breast cancer and are more likely to be diagnosed before menopause (Breast Cancer.org., 2012). To test for BRCA1 and BRCA2, a blood DNA sample is needed for full-length gene sequencing. A genomic profiling tool for breast cancer, approved in the United States, is specifically for estrogen-receptor–positive, node-negative breast cancer. One of the test results is a recurrence score, which correlates the chance of a specific tumor returning in the next 10 years. Genetic counseling is suggested before and after the workup (Townsend et al, 2012).

Once a mass is identified, the physician has multiple techniques to establish a diagnosis. During a fine-needle aspiration biopsy (FNAB) the physician or radiologist anesthetizes a small area of the breast with lidocaine. FNAB is mainly used for differentiation of solid from cystic masses but may also be performed when a new, dominant, unexplained mass is found in the breast. A 22- or 25-gauge needle attached to a 20-mL syringe is inserted into the mass, and a small amount of the contents is aspirated, then prepared on a slide for cytologic examination. Cyst fluid is usually cloudy and dark green or amber. If the mass is solid, the needle is repetitively inserted into the mass while steady negative pressure is applied to the syringe; suction is released and the needle is withdrawn. The slides are then fixed and submitted to pathology. Cytologic evaluation does not reveal if the cancer is invasive or noninvasive, so most physicians advise a core needle biopsy for histologic diagnosis before a surgical procedure (Townsend et al, 2012).

A core needle biopsy is similar to a FNAB but a larger needle is used because actual breast tissue is removed rather than a sampling of cells. Core needle biopsy is preferred over excisional biopsy because it is minimally invasive and less expensive (Townsend et al, 2012). The types of core biopsies are US-guided core biopsy and stereotactic core biopsy. US-guided core biopsy does not require surgery. A large biopsy needle is placed into the breast tissue and the US aids in confirming the proper needle placement for biopsy. US can also distinguish many benign lesions such as fluid-filled cysts. Tissue samples are then obtained through the needle. In stereotactic core biopsy, a large biopsy needle is inserted into the breast tissue; computerized mammographic pictures facilitate needle placement using digital imaging so the precise location of breast tissue is biopsied. Tissue samples are then withdrawn through the needle (Cleveland Clinic, 2009).

Surgical treatment ranges from minimally invasive breast biopsy, BCT, wide excision of the tumor mass, or modified radical mastectomy involving the breast and axillary lymph nodes. In some cases, salpingo-oophorectomy is considered (Domchek et al, 2010). BCT surgeries are alternately called segmental mastectomy, lumpectomy, partial mastectomy, wide local excision, and tylectomy (Hunt et al, 2010). The goal of surgery is removal of the cancerous mass with a margin of normal tissue and a good cosmetic result. When a specimen of breast tissue is sent to the laboratory, it is inked to mark the relationship between the tumor and the surgical margins of the excision. The pathologist evaluates these margins on all sides of the tumor for malignant cells. If a margin is positive it indicates that malignant cells may remain in the breast. Additional surgery is usually required until the margins contain only normal tissue (Stephan, 2009).

The choice of procedure depends on the size and site of the mass, the characteristics of the cells, the stage of the disease, and the patient’s choice. A breast cancer diagnosis is usually staged to measure the extent of the disease and to classify patients for possible treatment modalities (Figure 17-7 and Table 17-5). The TNM (T = tumor; N = node; M = metastasis) classification has been adopted as a mechanism to clinically stage this disease. Staging results are used in designing a specific treatment plan. Radiation therapy, chemotherapy, or hormonal therapy may be used with surgery or as alternative treatment methods. An intravenous (IV) access port may be surgically placed for later infusion of chemotherapeutic medications, fluids, or nutrition as well as to withdraw blood and laboratory specimens (Ambulatory Surgery Considerations).

Excised tumors or core needle biopsies are evaluated for their estrogen-binding and progesterone-binding abilities. Techniques have been developed to assess the ability of breast cancer to bind with estrogen and progesterone. This positive binding capability identifies the patient with a hormone-dependent tumor (Figure 17-8). It is estimated that about two thirds of all breast cancers are positive for estrogen binding, a majority of which are also positive for progesterone binding. The presence of these receptor sites is favorable to hormone manipulation, with the goal of preventing breast cancer cells from receiving estrogen stimulation. In these patients, who also have negative axillary nodes, it is decidedly preferable to obtain a genomic profile of the primary cancer to find out the risk for recurrence (Townsend et al, 2012). Use of selective estrogen receptor modulators (SERMs) and estrogen receptor down-regulators (ERDs), in addition to surgery and chemotherapy, increase disease-free survival in premenopausal women with positive binding for estrogen. Postmenopausal women benefit from aromatase inhibitors (AIs). They appear to work better than estrogen receptor modulators on certain breast cancers, with fewer side effects.

Some of the most promising data reported for advanced breast cancer involves human epidermal growth factor receptor 2 (HER-2), a cellular proto-oncogene coding for a transmembrane receptor. Agents such as trastuzumab (Herceptin), to target HER-2 were first approved for treatment of metastatic HER-2–positive breast cancer in 1998. In 2012, pertuzumab was approved for use in combination with trastuzumab and with the chemotherapy agent docetaxel (Baselga et al, 2012). It is indicated for use in patients with metastatic HER-2–positive breast cancer who have not received previous treatment with either chemotherapy or HER-2–targeted therapy. Research and understanding of the immune system, development of methods to evaluate aspects of the immune response, and ongoing development of monoclonal antibodies continue to transform the field of immunotherapy and breast cancer treatment (Modi, 2011).

Clinical trials are exploring the clinical effectiveness of poly ADP-ribose polymerase (PARP) enzyme inhibitors (Surgical Pharmacology) in triple-negative breast cancer (TNBC) patients. These tumors are estrogen and progesterone hormone receptor negative and HER-2/neu negative. TNBC is found in younger women, women of African American or Hispanic descent, and individuals with BRCA1 mutations. It also is associated with a worse prognosis than other breast cancer subtypes (Winer, 2011).

Surgical Pharmacology
Drugs Used in Breast Cancer

Medication Category	Dosage/Route	Purpose/Action	Adverse Reactions	Nursing Implications
Anastrozole Functional class: Antineoplastic Chemical class: Aromatase inhibitor	1 mg daily by mouth	Advanced breast cancer not responsive to other treatment in estrogen receptor–positive patients (usually postmenopausal), patients with advanced disease on tamoxifen, adjunct treatment in early breast cancer. Highly selective nonsteroidal aromatase inhibitor, lowers serum estradiol concentrations	Hot flushes, headaches, lightheadedness, nausea, vomiting, rash, leukopenia, chest pain, hypertension, edema, angina, myocardial infarction, cerebral infarct	Stevens-Johnson syndrome; take calcium and vitamin D for bone loss/fracture; increase in size of tumor and increased bone pain may occur and will subside rapidly.
Exemestane Functional class: Antineoplastic Chemical class: Aromatase inhibitor	25 mg by mouth after meals; may need 50 mg/day if taken with a potent CYP3A4 inducer	Advanced breast cancer not responsive to other therapies. Lowers serum estradiol concentrations	Headache, depression, insomnia, anxiety, fatigue, hot flushes, nausea, lymphopenia, dyspnea	Assess blood pressure for hypertension and bone mineral density; use reliable contraception; do not breastfeed.
Fulvestrant Functional class: Antineoplastic Chemical class: Estrogen receptor antagonist	500 mg on days 1, 15, 29, and monthly thereafter as an IM injection	Advanced breast cancer in estrogen receptor–positive patients	Headache, nausea, vomiting, rash	Encourage nutritious diet with iron and vitamins; store in refrigerator; report vaginal bleeding immediately; increase in size of tumor; use contraception.
Letrozole Functional class: Antineoplastic, nonsteroidal aromatase inhibitor	2.5 mg daily by mouth	Early advanced or metastatic breast cancer in postmenopausal women	Headache, lethargy, nausea, vomiting, anorexia, rash, pruritus, myocardial infarction (MI), cerebrovascular accident (CVA), endometrial carcinoma, vaginal bleeding, second malignancies	Regular assessment of hepatic function studies; may administer with bisphosphonates to increase bone density; nutritious diet with iron and vitamins; report vaginal bleeding.
Poly ADP-ribose polymerase (PARPs) inhibitors Functional class: Antineoplastic	Varies; 200 mg bid	Treat triple-negative breast cancer patients. Causes the BRCA genes to function improperly because of the mutation	Fatigue, somnolence, mood alteration	Report anything that may be considered a side effect; very little reported.
Raloxifene Functional class: Bone reabsorption inhibitor Chemical class: Hormone modifier, selective estrogen receptor modulator	60 mg daily by mouth	Breast cancer prevention, treatment of osteoporosis in postmenopausal women, breast cancer prophylaxis. Reduces resorption of bone and decreases bone turnover; mediated through estrogen receptor binding	Nausea, hot flushes, leg cramps, CVA, pulmonary embolism (PE), insomnia, peripheral edema, fever, weight gain	Regular hepatic studies done during therapy; bone density baseline obtained; administer vitamin D, calcium supplement; weigh weekly and report 5-lb weight gain; avoid staying in one position for long periods.
Tamoxifen Functional class: Antineoplastic Chemical class: Antiestrogen hormone	Breast cancer: 20 to 40 mg daily by mouth for 5 years High-risk breast cancer and DCIS: 20 mg daily by mouth for 5 years	Prevention of breast cancer following surgery or radiation; advanced breast cancer not responsive to other therapies in estrogen-positive patients. Inhibits cell division by binding to cytoplasmic estrogen receptors	Hot flushes, headache, lightheadedness, nausea, vomiting, rash, stroke, uterine malignancy, thrombocytopenia, PE, uterine malignancy, leukopenia	Do not break, crush, or chew tablets; obtain complete blood count (CBC) with differential and platelets regularly; encourage nutritious diet; increase fluids; routine eye exams.

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