Section 5. Breast

A 23-year-old woman, who is currently breastfeeding and 6 weeks postpartum, presents with a hard, red, tender, indurated area medial to her right nipple (Figure 92-1). She also has a low-grade fever. Because there is a local area of fluctuance, incision and drainage is recommended. The area is anesthetized with 1% lidocaine and epinephrine and drained with a #11 scalpel. A lot of purulence is expressed and the wound is packed. The patient is started on cephalexin 500 mg qid for 10 days to treat the surrounding cellulitis and seen in follow-up the next day. The patient was already feeling better the next day and went on to full resolution in the following weeks.

Mastitis, defined as an infection of the breast, and breast abscesses are typically found in breastfeeding women (Figure 92-1). A breast abscess and mastitis unrelated to pregnancy and breastfeeding can occur in older women (Figure 92-2).

• The prevalence of mastitis is estimated to be 2% to 3% of lactating women.1
• Breast abscess is an uncommon problem in breastfeeding women, with an incidence of approximately 0.1%.2

• Mastitis is most commonly caused by Staphylococcus aureus, Streptococcus species, and Escherichia coli.
• Recurrent mastitis can result from poor selection or incomplete use of antibiotic therapy, or failure to resolve underlying lactation management problems. Mastitis that repeatedly recurs in the same location, or does not respond to appropriate therapy, may indicate the presence of breast cancer.3

• Risk factors for mastitis include a history of mastitis with a previous child, cracks and nipple sores, use of an antifungal nipple cream in the same month, and use of a manual breast pump.4
• Risk factors for breast abscess include maternal age older than 30 years, primiparity, gestational age of 41 weeks, and mastitis.2,3 Breast abscess develops in 5% to 11% of women with mastitis, often caused by inadequate therapy.3

Clinical Features

• Mastitis causes a hard, red, tender, swollen area on the breast (Figures 92-1, 92-2, and 92-3). Erythema is less visible in darker skin but the swelling is still prominent (Figure 92-3).
• Usually unilateral, so the breast size difference can be obvious (Figure 92-3).
• Fever is common.
• Pain usually extends beyond the indurated area.
• It is often associated with other systemic complaints, including myalgia, chills, malaise, and flu-like symptoms.
• Breast abscess can occur with mastitis, except a fluctuant mass is palpable. (In Figure 92-2, the fluctuant mass is close to the midline with two openings of spontaneous drainage. The remainder of the erythema is the mastitis.)

• The typical distribution is usually unilateral.

Laboratory Testing

• In persistent cases, a mid-stream milk sample may be cultured and antibiotics prescribed based upon the identification and sensitivity of the specific pathogen.

Imaging

• Ultrasonography may be used to distinguish abscesses from other types of lesions. Abscesses appear as ill-defined masses and have central hypoechoic areas with either septations or low-level internal echoes, and posterior enhancement.5

Biopsy

• Biopsy is needed if a palpable mass remains after the infection is cleared.

• Mastitis should be distinguished from plugged lacrimal ducts, which present as hard, locally tender, red areas without associated regional pain or fever.
• Tinea corporis can cause erythema and scaling on any part of the body, including breast. It is often annular and pruritic (see Chapter 138, Tinea Corporis).
• Paget disease of the breast is an intraepithelial neoplasia that may appear as an erythematous patch on the nipple or breast (see Chapter 94, Paget Disease of the Breast).

Nonpharmacologic

• Management of mastitis includes supportive measures, such as analgesics, warm compresses, and continued breastfeeding. SOR C If the infant cannot relieve breast fullness during nursing, breast massage during nursing or pumping afterwards may help reduce discomfort.
• Frequent breast emptying helps both infectious and noninfectious mastitis.6 SOR A Breastfeeding may continue on both breasts if the incision isn't too painful and it does not interfere with the baby latching on. Otherwise a breast pump may be used on the affected breast for 3 to 4 days until nursing can resume.

Medications

• Acetaminophen or an antiinflammatory agent such as ibuprofen may be used for pain control.
• Antibiotic treatment should be initiated with dicloxacillin or cephalexin (500 mg PO 4 times daily) for 10 to 14 days.7 SOR A Consider clindamycin if the patient is allergic to penicillin and/or cephalosporins.7 Clindamycin 600 mg PO q6h may be a good choice if methicillin-resistant S. aureus (MRSA) is suspected. All of the antibiotics recommended are safe for the baby during pregnancy and lactation. Trimethoprim-sulfamethoxazole 1 DS tablet bid is an alternative for MRSA and/or penicillin-allergic patients, but it should be avoided near term pregnancy and in the first 2 months of breastfeeding because of a risk to the baby of kernicterus. Shorter courses of antibiotic therapy may be associated with higher relapse rates. SOR C
• For mastitis not associated with breastfeeding, use clindamycin 300 mg PO q6h, or amoxicillin/clavulanate 500 mg PO tid.8

Complementary and Alternative Therapy

• Preliminary data suggests that administration of lactobacilli strains that are naturally occurring in breast milk may be of therapeutic benefit for the management of mastitis during lactation.9 SOR C

Surgical

• The management of a breast abscess consists of drainage of the abscess.7 SOR A Antibiotic therapy should be considered and is especially important if there is surrounding cellulitis (see Figures 92-2 and 92-4).
• Drainage can usually be performed on abscesses smaller than 3 cm by needle aspiration, with the addition of ultrasound guidance if needed. Abscesses larger than 3 cm treated with needle aspiration have a high reoccurrence rate.10
• If needle aspiration is not effective, incision and drainage should be performed. Incision and drainage is often preferred because it allows for continued drainage through the opening. In many cases a cotton wick is placed to keep the abscess open while the purulence drains over the following days.

Referral or Hospitalization

• Hospitalization and intravenous antibiotics are rarely needed but should be considered if the patient is systemically ill and not able to tolerate oral antibiotics.

• If no response is seen within 48 hours or if MRSA is a possibility, antibiotic therapy should be switched to trimethoprim- sulfamethoxazole 1 DS tablet PO bid, or clindamycin 300 mg orally q6h. Avoid trimethoprim-sulfamethoxazole near term pregnancy and in the first 2 months of breastfeeding.

• The patient may take acetaminophen or ibuprofen for pain as these medications are safe while breastfeeding and are indicated for use in children.
• Warm compresses applied before and after feedings can provide some pain relief. A warm bath may also help.
• Instruct the patient to finish the antibiotic prescription, even if the patient feels better in a few days, to lower the risk of bacterial resistance or relapse.
• Continue feedings and, if necessary, use a breast pump to completely empty the breast.
• Educate the parents that the mastitis or the antibiotics will not harm the baby, and that the source of the infection was probably the baby's own mouth.
• Continue to drink plenty of water and eat well-balanced meals.

Patient Resources

• MedlinePlus. Breast Infection—http://www.nlm.nih.gov/medlineplus/ency/article/001490.htm.
• PubMed Health, Breast Infection—http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002460/.

Provider Resources

• Medscape. Breast Abscess and Masses—http://www.emedicine.com/EMERG/topic68.htm.
• Andolsek KM, Copeland JA. Benign breast conditions and disease: mastitis. In: Tayor RB, ed. Family Medicine Principles and Practice, 6th ed. New York: Springer; 2003:898.

A 55-year-old woman presents for routine screening mammogram. The patient does not have any complaints but has a family history of breast cancer in a sister at age of 40 years. Her mammogram demonstrates an irregular mass with possible local spread (Figures 93-1 and 93-2). She is referred to a breast surgeon and the biopsy confirms the diagnosis of breast cancer.

Breast cancer is a major health concern for all women. It is the most common female cancer in the United States, and the second most common cause of cancer death in women after lung cancer.1

• In 2007, approximately 178,000 women in the United States were diagnosed with breast cancer.1 Breast cancer incidence in the United States has doubled over the past 60 years. Since the early 1980s, most of the increase has been in early stage and in situ cancers because of mammogram screening (Figures 93-1, 93-2, 93-3, and 93-4).
• Approximately 232,620 new cases of invasive breast cancer were expected to be diagnosed in the United States in 2011, and 39,970 were expected to die from the disease.1
• Globally, breast cancer is the most common cancer, and the leading cause of cancer death in females. Breast cancer incidence rates are highest in North America, Australia-New Zealand, and Europe, and lowest in Asia and sub-Saharan Africa.2
• Locally advanced breast cancer (LABC) has been decreasing in frequency over the past several decades, at least partially as a result of earlier diagnosis because of better screening (Figures 93-5, 93-6, 93-7, and 93-8). It represents 30% to 50% of newly diagnosed breast cancers in medically underserved populations.3
• Primary inflammatory breast cancer (IBC) is relatively rare, accounting for 0.5% to 2% invasive breast cancers.4 However, it accounts for a greater proportion of cases presenting with more advanced disease. IBC is a clinical diagnosis. At presentation, almost all women with primary IBC have lymph node involvement and approximately one third have distant metastases.5

• The incidence of breast cancer increases with age. White women are more likely to develop breast cancer than black women. One percent of breast cancers occur in men.
• Primary risk factors for the development of breast cancer include age older than 50 years, female sex, increased exposure to estrogen (including early menarche and late menopause), and a family history in a first-degree maternal relative (especially if diagnosed premenopausally.).
• Approximately 8% of breast cancers are hereditary and of these one-half are associated with mutations in genes BRCA1 and BRCA2. It is more common in premenopausal women, multiple family generations, and bilateral breasts.6 Typically, several family members are affected over at least three generations and can include women from the paternal side of the family.
• A history of a proliferative breast abnormality, such as atypical hyperplasia, may increase a woman's risk for developing breast cancer.
• The selective estrogen receptor modulator tamoxifen (and possibly raloxifene) reduces the risk of developing breast cancer.
• The American Cancer Society, American College of Radiology, American Medical Association, and American College of Obstetrics and Gynecology all recommend starting routine screening at age 40 years.7
• The United States Preventive Services Task Force and the 2002 statement by the American Academy of Family Physicians recommend screening mammography every 1 to 2 years for women ages 40 years and older.8
• Women who have a family history of BRCA mutation should begin annual mammography between 25 and 35 years of age.9 SOR A
• MRI screening is more sensitive for detecting breast cancers than mammography and is being used to screen women with BRCA mutations.10 It is not proven that surveillance regimens that include MRI will reduce mortality from breast cancer in high-risk women.10
• Although the sensitivity of MRI is higher than that of conventional imaging. MRI has a lower specificity. One study suggests that unnecessary biopsies can be avoided with second-look ultrasound when MRI is positive and mammography is not. Second-look ultrasound can be used to recognize false-positive MRI results and guide biopsies.11

• Positive family history of breast and/or ovarian cancer (especially with BRCA mutations).
• Personal history of breast cancer.
• Increasing age in women.
• Early age at menarche and late menopause.
• Prolonged exposure to and higher concentrations of endogenous or exogenous estrogen.
• Exposure to ionizing radiation.
• Dense breast tissue and atypical hyperplasia.
• Women who have had no children or who had their first child after age 30 have a slightly higher breast cancer risk.
• Low physical activity levels.
• High-fat diet.
• Alcohol intake of two or more drinks daily.

Clinical Features

• Detection of a breast mass is the most common presenting breast complaint. However, 90% of all breast masses are caused by benign lesions. Breast pain is also a common presenting problem. Physical examination of the breast should be performed in the upright (sitting) and supine positions. Inspect for differences in size, retraction of the skin or nipple (Figures 93-5 and 93-6), prominent venous ­patterns, and signs of inflammation (Figures 93-5 and 93-6). ­Palpate the breast tissue, axillary area, and supraclavicular areas for masses or adenopathy. Gently squeeze the nipple to check for discharge.
• Most LABCs are both palpable and visible (Figures 93-7 and 93-8). Careful palpation of the skin, breasts, and regional lymph nodes is the initial step in diagnosis. The patient in Figure 93-8 had five palpable lymph nodes at the time of presentation.
• IBC usually presents clinically as a diffuse brawny induration of the skin of the breast with an erythematous edge, and usually without an underlying palpable mass. Patients with de novo IBC typically present with pain and a rapidly enlarging breast. The skin over the breast is warm, and thickened, with a “peau d'orange” (skin of an orange) appearance (Figures 93-5 and 93-6). The skin color can range from a pink flushed discoloration to a purplish hue.

Typical Distribution

• A mass that is suspicious for breast cancer is usually solitary, discrete, hard, unilateral, and nontender. It may be fixed to the skin or the chest wall.

Imaging

• More than 90% of breast cancers are identified mammographically.12 When an abnormality is found, supplemental mammographic views and possibly ultrasound are usually done. Diagnostic mammography is associated with higher sensitivity but lower specificity as compared to screening mammography.13

Biopsy

• Fine-needle aspiration biopsy generally uses a 20- to 23-gauge needle to obtain samples from a solid mass for cytology. Ultrasound or stereotactic guidance is used to assist in collecting a fine-needle aspiration from a nonpalpable lump. Core biopsy uses a 14-gauge or similar needle to remove cores of tissue from a mass. Excisional biopsy is done as the initial procedure or when needle biopsies are negative when the clinical suspicion is high. Guided biopsy and nonguided biopsy are also commonly used to make a definitive diagnosis.

• Fibroadenoma usually present as smooth, rounded, rubbery masses in women in their 20s and 30s. A clinically suspicious mass should be biopsied even if mammography findings are normal.
• Benign cysts are rubbery and hollow feeling in women in their 30s and 40s. A cyst can be diagnosed by ultrasound imaging. A simple cyst can be aspirated, but a residual mass requires further evaluation. Ultrasound is useful to differentiate between solid and cystic breast masses, especially in young women with dense breast tissue.
• Bilateral mastalgia is rarely associated with breast cancer, but it does not eliminate the possibility. It is usually related to fibrocystic changes in premenopausal women that are associated with diffuse lumpy breasts. A unilateral breast lump with pain must be evaluated for breast cancer.
• Nipple discharge may be from infection which is usually purulent, and from pregnancy, stimulation, or prolactinoma which produces a thin, milky, often bilateral discharge. A pregnancy test may be helpful. A suspicious discharge from a single duct can be evaluated with a ductogram.
• Infectious mastitis and breast abscess, which typically occur in lactating women, appear similar to IBC but are generally associated with fever and leukocytosis (see Chapter 92, Breast Abscess and Mastitis).
• Ductal ectasia with inflammation appears similar but is usually localized.
• Leukemic involvement of the breast may mimic IBC, but the peripheral blood smear is typically diagnostic.

Nonpharmacologic

• Surgical resection is required in all patients with invasive breast cancer. Oncologic outcomes are similar with mastectomy and breast conserving therapy (lumpectomy plus breast radiation therapy) in appropriately selected patients. For women undergoing mastectomy, breast reconstruction may be performed at the same time as the initial breast cancer surgery, or deferred to a later date.14 SOR A
• Long-term survival can be achieved in approximately 50% of women with LABC who are treated with a multimodality approach.15 Prognostic factors include age, menopausal status, tumor stage and histologic grade, clinical response to neoadjuvant therapy, and estrogen receptor status.
• In general, women with IBC are approached similarly to those with noninflammatory LABC except that breast conservation therapy is generally considered inappropriate for these women.16 SOR A

Medications

• Adjuvant systemic therapy consists of administration of hormone therapy, chemotherapy, and/or trastuzumab (a humanized monoclonal antibody directed against HER-2/neu) after definitive local therapy for breast cancer. It benefits most women with early stage breast cancer, but the magnitude of benefit is greatest for those with node-positive disease.17 SOR A
• The most common approach for advanced breast cancer is preoperative chemotherapy followed by surgery and radiotherapy. Questions regarding sequencing and choice of specific chemotherapy regimens and extent of surgery (including the utility of the sentinel node biopsy) persist. SOR A
• Preoperative (as opposed to postoperative) chemotherapy has several advantages for advanced breast cancer (Figure 93-7) treatment. It can reduce the size of the primary tumor, thus allowing for breast conserving surgery, permits assessing an identified mass to determine the sensitivity of the tumor cells to drugs with discontinuation of ineffective therapy (thus avoiding unnecessary toxicity), and enables drug delivery through an intact tumor vasculature.18 SOR A
• Tamoxifen and aromatase inhibitors may be used in selective patients as neoadjuvant hormone therapy of decrease overall tumor volume. SOR A

Referral or Hospitalization

• With the emergence of breast-conserving therapy (BCT), many women now have the option of preserving a cosmetically acceptable breast without sacrificing survival for early stage invasive breast cancer.

• Healthy lifestyle choices can decrease the risk of breast cancer, including a low-fat diet, regular exercise, and no more than one drink daily.
• Having children before age 30 years and prolonged breastfeeding may be of help in primary prevention, but will not be a commonly used strategy for most women.
• Secondary prevention involves screening for breast cancer with physical exams and mammography. There is a strong consensus based on consistent findings from multiple randomized trials that routine screening mammography should be offered to women ages 50 to 69 years. Consensus is less strong for routine screening among women ages 40 to 49 years, women older than age 70 years, or for how frequently to screen.
  • The American Cancer Society,19 the National Cancer Institute,20 the American College of Obstetricians and Gynecologists,21 and the National Comprehensive Cancer Network22 recommend starting routine screening at age 40 years.
  • The United States Preventive Services Task Force (USPSTF)23 and the Canadian Task Force on the Periodic Health Examination24 recommend beginning routine screening at age 50 years.
• Prophylactic mastectomy is an effective and accepted method by some BRCA-positive women after childbearing when their risk of lifetime breast cancer without this intervention is high (e.g., over 60%).
• Chemoprevention with tamoxifen or raloxifene is an option for women who are high risk for breast cancer.

• Regular follow-up will usually be maintained during treatment. After treatment, life-long regular follow-up for surveillance should be maintained. Metastases can present in many ways including difficulty breathing, back pain, or a new skin nodule (Figure 93-9). These complaints should be taken seriously and worked up carefully in any patient with a history of breast cancer.

• The contralateral breast is at increased risk of breast cancer and should be monitored. Patients on tamoxifen should be monitored for endometrial hyperplasia or cancer.

Patient Resources

• Breast cancer support group for survivors—http://bcsupport.org/.
• Breastcancer.org—http://www.breastcancer.org/.

Provider Resources

• American Academy of Family Physicians. Breast Cancer—http://www.aafp.org/online/en/home/clinical/exam/breastcancer.html.
• U.S. Preventive Services Task Force. Screening for BreastCancer—http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm.
• National Cancer Institute. Breast Cancer—http://www.cancer.gov/cancertopics/types/breast.

A 62-year-old woman presents with a 6-month history of an eczematous, scaly, rash near her nipple. It is mildly pruritic. On physical examination, the nipple and the areola are involved (Figure 94-1). Also, a hard mass is present in the lateral lower quadrant of the same breast. A 4-mm punch biopsy of the affected area including the nipple demonstrates Paget disease. The mammogram is suspicious for breast cancer at the site of the mass and the patient is referred to a breast surgeon.

Paget disease of the breast is a low-grade malignancy of the breast that is often associated with other malignancies. It is an important consideration when working up a chronic persistent abnormality of the nipple.

Paget's disease, Mammary Paget disease.

• The incidence of Paget disease of the breast is approximately 0.6% in women in the United States, according to National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) data.1 Paget disease, like all breast cancers, is rare in men.
• The peak incidence is between 50 and 60 years of age.2
• It is associated with underlying in situ and/or invasive breast cancer 85% to 88% of the time.3

• Most patients delay presentation, assuming the abnormality is a benign condition of some sort. The median duration of signs and symptoms prior to diagnosis is 6 to 8 months.2
• Presenting symptoms are sometimes limited to persistent pain, burning, and/or pruritus of the nipple (Figures 94-1 and 94-2).
• A palpable breast mass is present in 50% of cases, but is often located more than 2 cm from the nipple–areolar complex.4
• Twenty percent of cases will have a mammographic abnormality without a palpable mass, and 25% of cases will have neither a mass nor abnormal mammogram, but will have an occult ductal carcinoma.
• In less than 5% of cases, Paget disease of the breast is an isolated finding.4
• There are two theories regarding the pathogenesis of Paget disease of the breast, the choice of which affects treatment choices.
  • The more widely accepted epidermotropic theory proposes that the Paget cells arise from an underlying mammary adenocarcinoma that migrates through the ductal system of the breast to the skin of the nipple. It is supported by the fact that Paget disease is usually associated with an underlying ductal carcinoma, and both Paget cells and mammary ductal cells usually express similar immunochemical staining patterns and molecular markers. This could mean that there is a common genetic alteration and/or a common progenitor cell for both Paget cells and the underlying ductal carcinoma.
  • The less widely accepted transformation theory proposes that epidermal cells in the nipple transform into malignant Paget cells, and that Paget disease of the breast represents an independent epidermal carcinoma in situ. It is supported by the fact that there is no parenchymal cancer identified in a small percentage of cases, and underlying breast carcinomas are often located at some distance to the nipple. Most pathologists disagree with the transformation theory.

Clinical Features

• Paget disease of the breast presents clinically in the nipple-areolar complex as a dermatitis that may be erythematous, eczematous, scaly, raw, vesicular, or ulcerated (Figures 94-1, 94-2, 94-3, and 94-4). The nipple is usually initially involved, and the lesion then spreads to the areola. Spontaneous improvement or healing of the nipple dermatitis can occur and should not be taken as an indication that Paget disease is not present. The diagnosis is made by finding malignant, intraepithelial adenocarcinoma cells on pathology. Rarely, nipple retraction is found.
• Pain, burning, and/or pruritus may be present or even precede clinically apparent disease develops on the skin.

Typical Distribution

• Paget disease of the breast is almost always unilateral, although bilateral cases have been reported.
• Work-up must also be directed toward identifying any underlying breast cancer.

Laboratory Testing

• The diagnosis is made by finding intraepithelial adenocarcinoma cells (Paget cells) either singly or in small groups within the epidermis of the nipple complex.

Imaging

• Bilateral mammography is mandatory to asses for associated cancers. MRI may disclose occult cancer in some women with Paget disease of the breast and normal mammography and/or physical examination.5

Biopsy

• The diagnosis is usually made by full-thickness punch or wedge biopsy that shows Paget cells. Nipple scrape cytology can diagnose Paget disease and may be considered for screening eczematous lesion of the nipple.

• Eczema of the areola is the most common cause of scaling of the breast (Figure 94-5). If the patient (Figure 94-5) had new nipple inversion with the onset of skin changes, this would be more suspicious for Paget disease.
• Bowen disease is squamous cell carcinoma in situ and can differentiate from Paget disease by histology. Also, Bowen disease expresses high-molecular-weight keratins, whereas Paget disease expresses low-molecular-weight keratins (see Chapter 166, Actinic Keratosis and Bowen Disease and Chapter 171, Squamous Cell Carcinoma).
• Superficial spreading malignant melanoma may be confused with Paget disease but histologic study and immunohistochemical staining can separate the two (Figure 94-6) (see Chapter 172, Melanoma).
• Seborrheic keratoses and benign lichenoid keratoses can occur on and around the areola and be suspicious for Paget disease (Figure 94-7). A biopsy is the best way to make the diagnosis (see Chapter 158, Seborrheic Keratosis).
• Nipple adenoma, which usually presents as an isolated mass with redness, can be diagnosed with biopsy.

Surgical

• The treatment and prognosis of Paget disease of the breast is first based on the stage of any underlying breast cancer. Simple mastectomy has traditionally been the standard treatment for isolated Paget disease of the breast, but breast-conserving treatment is being used more often. Breast-conserving surgery combined with breast irradiation is gaining wider acceptance. The surgically conservative approaches include excision of the complete nipple-areolar complex with margin evaluation. Sentinel lymph node biopsy should be performed to evaluate axillary lymph node status.6 SOR B

• Patients with only noninvasive Paget disease of the nipple have excellent cancer outcome with conservative surgery, with survival rates similar to those achieved with mastectomy.7,8 SOR B The prognosis of Paget disease with synchronous cancer is dependent upon the tumor stage of the underlying cancer.

• All lesions of the breast that do not heal should be checked for cancer.
• The patient's prognosis is based on the underlying cancer, if present, not the Paget disease itself.

Patient Resources

• Breastcancer.org. Paget Disease of the Nipple—www.breastcancer.org/symptoms/types/pagets/.
• Imaginis. Paget Disease of the Nipple—http://imaginis.com/breasthealth/pagets_disease.asp.
• Macmillan Cancer Support. Paget Disease of the Breast—http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Breast/Aboutbreastcancer/Typesandrelatedconditions/Pagetsdisease.aspx.

Provider Resources

• Medscape. Mammary Paget Disease—http://emedicine.medscape.com/article/1101235-overview.
• National Cancer Institute. Paget Disease of the Nipple—http://www.cancer.gov/cancertopics/factsheet/Sites-Types/pagets-breast.