Physical exam findings of benign breast masses can be hard to differentiate from cancer, since a normal variant of breast tissue can feel to be nodular. A careful inspection for asymmetry, skin changes, and nipple discharge (or crusting) should be done for each patient reporting a newly found breast mass. A bimanual examination of the breasts should then be performed with the patient in a supine position, with the ipsilateral arm raised above her head, palpating for any obvious masses. A single dominant lesion that is hard, immobile, and with irregular borders is suspicious for breast cancer. The cervical, supraclavicular, infraclavicular, and axillary nodes should also be examined. Enlarged, firm, immobile, and/or matted lymph nodes suggest disseminated cancer.

The most important risk factors for breast cancer are female gender, increasing age, and a family history of premenopausal breast cancer. In particular, a family history of breast cancer in males or premenopausal women, bilateral breast cancer, a history of ovarian cancer, and multiple relatives with cancer should prompt investigation for the presence of a gene mutation. The majority of inherited breast cancers are associated with BRCA1 or BRCA2 gene mutations. Other important risk factors associated with a slightly higher risk of developing breast cancer include diethylstilbestrol (DES) exposure, early menarche, nulliparity or childbirth after age 30, and/or late menopause. Table 3.1 shows the relative risk of developing breast cancer for certain risk factors.

Nipple discharge is categorized as normal milk production (lactation), physiologic nipple discharge, or pathologic nipple discharge. Benign nipple discharge tends to be clear, bilateral, and multiductal. Physiologic discharge can be related to post-lactation (up to 2 years following birth), fluctuating hormone levels (puberty and menopause), or nipple stimulation. Pathologic nipple discharge can be due to medical conditions such as prolactinoma, hypothyroidism (thyroid-releasing hormone stimulates prolactin), Cushing’s disease, or medications (e.g., antipsychotics, cimetidine, spironolactone). A common cause of pathologic nipple discharge (unilateral, bloody) is a papilloma, which is a tumor growing from the lining of the breast duct. Nevertheless, malignancy can be found in up to 15 % of patients that present with nipple discharge. Cancer is more likely if the discharge is bloody, spontaneous, unilateral, uniductal, associated with a breast mass, or occurs in women over 40.

Most cases of fibrocystic-related changes are benign, but certain features place patients at an increased risk for invasive carcinoma in both breasts. Apocrine metaplasia has no increased risk for cancer. Ductal hyperplasia or sclerosing adenosis doubles the risk of cancer development. Atypical hyperplasia has the highest risk for cancer.

Peau d’orange is derived from French translation (orange skin). When lymph drainage in the breast is compromised by a tumor, it can result in edema expanding the interfollicular dermis, producing characteristic dimples which resemble the texture and appearance of orange peels. When deeper subcutaneous layers are involved, it can also cause pitting. This finding is most commonly seen in inflammatory carcinoma. A full-thickness, punch biopsy of the dermis is essential for definitive diagnosis.

The suspensory ligaments of the breasts are called Cooper’s ligaments. When a breast tumor infiltrates these ligaments, it can retract the skin, often at or around the nipples.

The “triple test” is a clinical tool that should be applied to all newly detected breast masses. This includes careful physical examination, imaging, and tissue sampling, with each test classified as benign (1 point), suspicious (2 points), or malignant (3 points). A range from 3 to 9 can help stratify patients into groups that are likely benign to a high likelihood of malignancy.

The recommended imaging depends on the age of the patient. The breasts of younger women consist of dense, fibrous tissue, and as such, mammography is not as useful in detecting abnormalities. In addition, most breast masses in women under 30 are benign, so it is best to avoid unnecessary radiation. Therefore, ultrasound is the first line of imaging in a woman who is pregnant or less than 30 years old with focal breast findings. Ultrasound can differentiate a cystic mass from a solid mass and can be used for needle-guided aspiration if indicated. If the mass is a simple cyst, it can be observed. If the cyst is painful or enlarging, it should be aspirated. If the fluid is bloody, it should be sent for cytology. If the mass is solid, a biopsy should be performed. The diagnostic procedure of choice is core needle biopsy rather than surgical biopsy. Breast magnetic resonance imaging (MRI) is not indicated for the workup of a new breast mass, but is reserved for diagnostic dilemmas. Note that breast MRI has a high false-positive rate.

A diagnostic mammogram should be the first test ordered in a woman over the age of 30 with a new breast mass to better characterize the mass, identify other non-palpable lesions in the affected breast, as well as examine the contralateral breast. Certain mammographic features such as asymmetry, clustered pleomorphic calcification, increasing density, or a new mass with irregular borders or spiculation are suggestive of malignancy. Once a mass is identified, a core needle biopsy (ultrasound-guided, if necessary) should be performed to exclude cancer, regardless of mammogram results (Fig. 3.1).

For clinically early stage breast cancer, an extensive metastatic work up is not needed. Laboratory tests are obtained to search for evidence of liver (liver chemistries) or bone (alkaline phosphatase, serum calcium) metastasis. A chest X-ray is obtained to determine the presence of pulmonary metastasis. Routine abdominal and chest CT are not recommended (unless symptomatic or laboratory values or plain chest X-ray are abnormal). Similarly, bone scintigraphy is only obtained if driven by abnormal lab values or the presence of suspicious bone pain. Likewise, the use of brain CT or MRI is symptom-driven (new onset headaches, vision changes, or seizures). PET scan is also not routinely ordered. For those who on physical exam have a clinically advanced breast cancer (stage 3), a more extensive metastatic workup is recommended, including CT of the chest, abdomen, and pelvis, as well as a bone scan.

The most commonly used staging system (Table 3.2) is the one described by the American Joint Committee on Cancer (AJCC). T (tumor) describes the size of the tumor and/or its depth of invasion. N (node) describes spread to regional lymph nodes. M (metastasis) indicates if the tumor has metastasized remotely.