Given a set of risk factors, what is the probability that a woman will develop breast cancer during the next 5 years and by age 90 years? While there are several models such as Gail [5], Claus [6], or Tyrer-Cuzick [7] that estimate breast cancer risk, the Gail model is the more widely known. The most updated version of the Gail model has been implemented into a variety of formats, one of which is the Breast Cancer Risk Assessment Tool (BCRAT); BCRAT is available on the National Cancer Institute (NCI) website (http://​cancer.​gov/​bcrisktool). The BCRAT incorporates information such as patient’s age, age at menarche, age at first live birth, number of 1st degree relatives with breast cancer, number of prior breast biopsies, presence of atypia on biopsy, and race/ethnicity. Such a model informs the patient and her health-care providers of her risk and allows them an opportunity to select appropriate management options to reduce such a risk.

The female adult breast is arranged into 15–20 lobes, with each lobe made up of many smaller lobules. The lobules are all linked by ducts, which terminates in the nipple. Adipose tissue fills the spaces between lobules and ducts (Fig. 4.1). Each breast contains a rich network of blood vessels and lymphatics, the latter drains into the axilla, supraclavicular region, internal mammary lymph nodes, as well as other parts of the body (Fig. 4.2).

Breast cancer encompasses a variety of histologies including ductal, lobular, medullary, tubular, and metaplastic. Of these, invasive ductal carcinoma (IDC) is the most common, accounting for about 80 % of the cases [8, 9] (Fig. 4.3v). Invasive lobular carcinoma (ILC) is the second most common, accounting for about 8–15 % of all invasive breast cancer [8, 10]. ILC typically arranges itself in a linear arrangement (single-file pattern), has a tendency to grow around ducts and lobules in a circumferential manner, and is associated with desmoplastic stromal reaction (Fig. 4.3b). Compared to IDC, ILC tends to be well differentiated; has a lower rate of HER-2 overexpression [11], higher rate of hormone receptor positivity [10], and higher incidence of bilaterality, multifocality, and multicentricity [12, 13]; and is more likely to harbor micrometastatic disease [14]. Other histologic types that are associated with a good prognosis are medullary, mucinous, tubular, cribriform, and adenoid cystic carcinoma of the breast, while micropapillary carcinoma and angiosarcoma are the more aggressive subtypes (Fig. 4.3c–f). Regardless of the subtypes, treatment is the same for all because current treatment guidelines and decision strategies are not dependent on subtypes.

Once a diagnosis of breast has been made, the clinician should ask the following important questions: am I dealing with (1) an operable or early breast cancer (EBC), (2) locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC), or (3) metastatic breast cancer? This is important because the answer will help guide her/him in selecting the most appropriate treatment option.

The answer to be above question is based on the clinician’s initial assessment of the patient’s clinical presentation. This is referred to as the clinical stage, which is different from the pathologic stage; the latter is based on the final pathology after the definitive operation. There are occasions whereby the clinician’s initial impression may be discordant with the pathologic stage (i.e., clinical impression that the patient has an EBC, but in actuality, she has advanced stage breast cancer). Regardless, the initial treatment of the patient is still predicated on the initial clinical examination. An example is a woman who presents with a breast mass that measures approximately 2.5 cm (T2) and without evidence of axillary lymphadenopathy on clinical examination (N0). Her clinical stage at this point is Stage 2 (T2N0). After undergoing definitive surgery, the final pathology demonstrated a 2.5 cm cancer (T2) with 5 out of 15 lymph nodes involved with metastatic tumor (N2). Therefore, her pathologic stage is Stage 3 (T2N2).

To determine the clinical stage, the size of the tumor and the status of the axilla should be documented. For asymptomatic patients with EBC, no further metastatic work-up is necessary. However, respiratory and neurologic complaints, bone pain, etc. necessitate a metastatic work-up. The American Joint Committee on Cancer (AJCC) TNM staging system, 7th edition, is used to stage patients with EBC [15] (Table 4.2).

In treating patients with EBC, the clinician needs to address the following: (1) local control (the primary breast tumor and the at-risk ipsilateral breast), (2) regional control (axillary lymph nodes), and (3) distant control (systemic disease). In general, the surgeon, along with her/his radiation oncologist, is responsible for the first two considerations, while her/his medical oncology colleague is responsible for the third.

Patients often present with an abnormal mammogram or breast ultrasound, with or without a palpable mass. In addition, complaints of breast pain, nipple discharge, or a palpable breast mass may also be the reasons why a patient would seek medical counseling. The initial evaluation consists of a complete history and physical examination, focusing mainly on the risk factors for breast cancer (see above), including a gynecologic history, and thoroughly examining the breast.

If the patient has no imaging, a mammogram or an ultrasound should be ordered. The most recent imaging studies should be compared with prior studies. A thorough review of the patient’s mammogram and/or breast ultrasound should be done with a radiologist. Breast ultrasound is useful for younger women (<40 years old) who tend to have denser breast tissue than older women. In some situations, both a mammogram and ultrasound might be necessary to complete the evaluation.

Classic mammographic abnormalities that are highly suggestive of a malignancy include an abnormality with irregular or spiculated borders, architectural distortion, or suspicious calcifications (linear, branching, ductally oriented, pleomorphic, clustered) (Fig. 4.4). For ultrasound, the following features are worrisome for malignancy: hypoechoic, posterior shadowing, irregular borders, nonparallel orientation, and asymmetry (Fig. 4.5).

The American College of Radiology (ACR) has developed a standardized system of describing mammographic and ultrasound readings. The system, the Breast Imaging Reporting and Data System (BI-RADS), groups the findings into categories numbering from 0 through 6. In general, BI-RADS 0 requires additional imaging, BI-RADS 1 and 2 can be observed with annual mammogram, BI-RADS 3 requires a repeat mammogram 6 months and thereafter until the finding is known to be stable (usually at least 2 years), BI-RADS 4 and 5 require a biopsy, and BI-RADS 6 is a biopsy-proven cancer (a mammogram usually obtained after a known cancer by a previous biopsy; the mammogram, in such a case, may be used to see how sensitive the cancer is to systemic therapy) (Table 4.3). Of note, mammograms have a 10 % false-negative rate. Thus, clinical suspicion should prompt the clinician to pursue a more intense investigation despite a negative mammographic reading. On occasions, there may be discordance between the BI-RADS assignments for the mammogram and ultrasound (i.e., BI-RADS 3 for mammogram and BI-RADS 4 for ultrasound). In such a situation, we recommend to err on the conservative side and proceed with the work-up based on the highest BI-RADS reading.

A brief mentioned of screening MRI of the breast is warranted. There are no randomized trials available to determine whether screening MRI reduces mortality from breast cancer. However, screening MRI is thought to be cost effective for women between ages 30 and 60 years who either carry a BRCA mutation or have a 50 % chance of carrying such a mutation [17]. The estimated cost per quality-adjusted life-year (QALY) gained in this group is approximately $55,420–$130,625 (i.e., it costs this much per additional life-year per person). Although there is no absolute QALY threshold, in the United States, it is thought to be around $50,000–$100,000 per QALY gained, while in the United Kingdom, it is approximated to be around $30,000–$45,000 [18].

The American Cancer Society (ACS), endorsed by ACR and Society of Breast Imaging (SBI) [19], recommends annual MRI screening, along with mammography, for women at high lifetime risk (≥20 %) of developing breast cancer, beginning at age 30. The lifetime risk can be calculated using the already mentioned risk estimation models, although ACS does not recommend using the Gail model because it does not incorporate family history of ovarian or breast cancer in 2nd-degree relatives [20]; high lifetime risk includes patients with known BRCA1 or BRCA2 gene mutation or who have a 1st-degree relative with a BRCA1 or BRCA2 gene mutation and history of radiation to the chest at the ages between 10 and 30 years and patients with Li-Fraumeni syndrome or Cowden syndrome or who have a 1st-degree relative with one of these syndromes [21]. For those who are at a moderate risk of developing breast cancer (15–20 % lifetime risk), it is recommended that they discuss screening MRIs with their physicians. Moderate risk group includes those who have a personal history of breast cancer, DCIS, LCIS, ADH, atypical lobular hyperplasia, or those with extremely dense breasts or unevenly dense breasts seen on mammograms. Low-risk group includes those whose lifetime risk of breast cancer is less than 15 %; routine screening MRI is not recommended [22]. Screening MRIs should be done in a facility that also has the capability of performing an MRI-guided breast biopsy (Table 4.4). It must be stressed that MRI is not meant to replace mammography and that the guidelines are not intended to replace sound clinical judgment or considered standard of care.

Routine preoperative MRI should not be used in all cancer patients since it has no significant impact on outcome. A recent meta-analysis found that preoperative MRI for staging breast cancer did not reduce the risk of local ipsilateral recurrence and distant recurrence [22]. Additionally, preoperative MRI not only fails to reduce re-excisions rate [23], it increases the odds of a patient receiving a mastectomy who would otherwise be a candidate for a BCT [24].

Breast masses can be cystic, solid, or both. Cystic masses can be aspirated with a fine-needle aspiration (FNA), guided either by palpation or ultrasound (US). Non-bloody aspirate can be discarded unless there is a clinical or radiologic suspicion of an associated malignancy. For non-cystic abnormality, the selection of the most appropriate biopsy technique will depend on whether the abnormality is palpable or non-palpable. Excisional biopsy as the initial diagnostic tool should be avoided unless minimally invasive biopsy techniques (percutaneous image-guided biopsy or palpation-guided) are not available. In general, a percutaneous biopsy such as a core needle biopsy (CNB) with either a 12–14 gauge needle or vacuum-assisted biopsy with a 7–11 gauge needle is the preferred initial diagnostic procedure for both palpable and non-palpable lesions [25]. If the biopsy is positive for either noninvasive cancer (DCIS; see Chap. 3) or invasive cancer, the clinician can then provide the patient with an optimal plan of care, which can include a single trip to the operating room for a definitive surgery. If it is negative or nondiagnostic, then the result should be put in context with the clinical examination and radiologic imaging. If the clinical exam and radiologic imaging are in concordance with the biopsy result (triple concordance), then the likelihood of a missed malignancy is very low (accuracy ranges from 93 to 99 %). However, if there is any discordance (i.e., lesion is suspicious for malignancy based on clinical exam and/or radiologic imaging), then the lesion should be excised for a definitive diagnosis (i.e., excisional biopsy for palpable lesion, needle localization biopsy for non-palpable lesion). Curvilinear incisions following Langer’s skin lines should be considered for optimal cosmesis (Fig. 4.6), and the pathologic specimen should be appropriately oriented. Specimens should be marked in a consistent manner to avoid confusion by the pathologist about the proper orientation, which could influence appropriate re-excision to achieve negative margins. Although a commonly used method calls for a short stitch be placed to designate the superior margin and a long stitch to indicate the lateral margin, this two-stitch method has been shown to be associated with an error rate of 31 % [26]. Intraoperative inking by the surgeon or placement of at least three separate marking sutures/clips for specimen orientation is recommended.

For patients with high-risk lesions such as atypical ductal hyperplasia (ADH), atypical lobular hyperplasia, lobular carcinoma in situ, and radial scars (complex sclerosing lesions) found on percutaneous biopsy, a surgical excision should be performed to assure that no occult DCIS or invasive cancer is present [25]. Of note, if a percutaneous biopsy will remove most or all of the abnormality, then a clip or some other imaging marker should be inserted at the time of biopsy.