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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Breast cancer is the second most common cancer in women after skin cancer. Most breast cancers are , which start in the milk ducts or lobules.

Factors associated with an increased risk for breast cancer include:

• Age: Risk increases with advancing age; only 9% of breast cancers occur in women younger than 45, and the average age of a patient with breast cancer is 62.

• Reproductive factors: Early menarche, parity, older age at first full-term pregnancy, lack of breastfeeding, high levels of circulating testosterone after menopause, late-onset menopause.

• Lifestyle: Smoking, alcohol use, low intake of fruits and vegetables, overweight/obesity, physical inactivity/sedentary lifestyle.

• Hormone exposure: Use of hormone-replacement therapy (HRT), particularly combined estrogen-progestin after menopause, and starting HRT closer to menopause.

• Genetic predisposition: High-risk inherited mutations BRCA1, BRCA2, TP53, PTEN, STK11, ATM, BARD1, BRIP1, CHEK2, CDH1, NF1, PALB2, PTEN, RAD51C, and RAD51D.

Other risk factors, according to the :

• Personal history of breast cancer or certain non-cancerous breast diseases: Women who have had breast cancer are more likely to get breast cancer a second time. Some non-cancerous breast diseases such as atypical hyperplasia or lobular carcinoma in situ are associated with a higher risk of getting breast cancer.

• Family history of breast or ovarian cancer: A woman's risk for breast cancer is higher if she has a mother, sister, or daughter (first-degree relative) or multiple family members on either her mother's or father's side of the family who have had breast or ovarian cancer. Having a first-degree male relative with breast cancer also raises a woman's risk.

• Previous treatment using radiation therapy: Women who had radiation therapy to the chest or breasts (for example, for treatment of Hodgkin's lymphoma) before age 30 have a higher risk of getting breast cancer later in life.

• Exposure to the drug diethylstilbestrol (DES): Given to some pregnant women in the U.S. from 1940 through 1971 to prevent miscarriage. Women who took DES, or whose mothers took DES while pregnant with them, have a higher risk of getting breast cancer.

Detection and Diagnosis

Regarding breast self-examination, the that although evidence does not show that regular breast self-exams help reduce deaths from breast cancer, it is important for women to be familiar with their normal anatomy so they can become aware of any changes and then report any changes to a healthcare provider right away. This is especially important if a woman notices a breast change between her regular mammograms.

Clinical history should evaluate breast cancer risk and assess for the presence or absence of symptoms that may be indicative of breast disease. Physical examination should include a thorough visual inspection with the patient sitting upright and looking down, looking for nipple changes, asymmetry, and obvious masses. The nipple-areola complex and each quadrant of both breasts should be palpated systematically.

Breast cancer screening is the mainstay imaging tool for early detection of non-palpable masses. Screening guidelines vary, but generally recommend annual or biannual screening,

MRI and ultrasound can be used as diagnostic adjunctive imaging in select patient groups. MRI is suggested for women with a high risk for breast cancer.

Based on imaging results, a patient may require a surgical or core-needle biopsy to make a definitive diagnosis. Factors that assist in the determination of which biopsy to use are appearance, size, and location of the suspicious area on the breast.

Surgical biopsy data will provide more information on the type, grade, and receptor status of the tumor, the distance between the surrounding normal tissue and the excised tumor, and the tumor margin.

Receptor Status

Breast cancers may be positive for estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2-neu (HER2/neu). Specific receptor status can be determined by immunohistochemistry testing or fluorescence in situ hybridization.

Breast cancer is categorized into subtypes based on the presence or absence of molecular markers for ER, PR, and HER2. The majority of patients are hormone receptor-positive/HER2 negative. Triple-negative breast cancer, which refers to disease that lacks all three of these receptors, accounts for about 15% of cases and is a more aggressive subtype.

Management

After initial diagnosis, a patient is clinically staged using the . Anatomical staging looks at primary tumor size (T), lymph node involvement (N), and metastasis (M). Anatomic TNM staging is further categorized into pretreatment clinical staging, pathologic staging after surgical intervention, and post-neoadjuvant therapy staging after preoperative systemic or radiation therapy.

Prognostic staging incorporates tumor grade, hormone receptor and oncogene status, and multigene panel results.

The general stages of breast cancer are the following:

• Stage 0: Noninvasive cancer or precancer

• Stage I: Very early invasive cancer, with substages based on tumor size and lymph node status

• Stage II: Cancer in a limited region of the breast that has grown larger, with substage based on tumor size and lymph node status

• Stage III: Cancer has spread further into the breast, or the tumor is a larger size than in earlier stages, with substage based on tumor size and number of lymph nodes involved

• Stage IV: Advanced cancer has spread to nearby lymph nodes and has spread beyond the breast to other areas of the body

For stage IV, or metastatic, breast cancer, tumor- and patient-level factors are prognostically important. Visceral metastases, brain metastases, and multiple metastatic sites confer worse prognosis. A better performance status, younger age at diagnosis, metastatic disease only to the bone, and a longer disease-free interval between initial diagnosis and development of metastatic recurrence all confer better prognosis.

Management requires a multidisciplinary team of, among many others, breast surgeons, medical oncologists, radiation oncologists, nurses, geneticists, and reconstructive surgeons. A less invasive surgical approach to staging and management of the axilla is desirable in select patients, while molecular and genomic profiling is key for the treatment of a biologically heterogenous disease. A multidisciplinary tumor board may review a case. Such boards are composed of different clinical specialists who work together to make shared decisions on the clinical pathway of patients.

Treatment of Early Stage Breast Cancer

With the completion of diagnostic and staging tests (CT, PET, bone scan), clinicians can begin discussing treatment options with the patient, such as:

• Local treatment: Breast-conserving surgery or mastectomy, external-beam radiation therapy, surgical management of the axillary lymph nodes independent of surgical therapy of the breast

• Systemic treatment: Chemotherapy, hormone therapy, targeted drug therapy, immunotherapy

• Treatment approaches: By cancer stage and/or based on the absence or presence of molecular markers

Epidemiologic Trends, Geographic Variations

from the U.S. Surveillance, Epidemiology, and End Results database showed an increased incidence of breast cancer among all races and decreased mortality among all races.

More specifically, the highest decrease in mortality was seen among white patients, with the highest decrease in breast cancer rates from 2016 to 2018.

Among Black patients, the overall incidence-based mortality decreased, with the highest decrease in rates from 2016 to 2018. In Hispanics/Latinos, the overall incidence-based mortality decreased at a rate that was still lower than that seen in white patients.

Breast cancer incidence-based mortality rates were highest among those over age 40, among Black patients, and among those with localized stage disease.

Multiple risk factors are believed to add to the increasing incidence of breast cancer in the U.S., including obesity, particularly in postmenopausal women, which is also linked to worse outcomes for breast cancer patients of all ages.

Many studies also show that have an increased risk of breast cancer. For example, an found that for each alcoholic drink consumed per day, the relative risk of breast cancer increased by about 7%.

A . The average age that U.S. women had their first child has increased over the last approximately 60 years from ages 23 to 27. This delay means that women have higher estrogen exposure over their lifetime, increasing the chance of developing breast cancer.

There are also geographically based disparities in breast cancer incidence. For instance, U.S. counties with higher concentrations of ethnic and/or racial minorities and lower concentrations of white women were deemed "hot spots," or high-rate cancer cluster centers.

Inhabitants of persistent "hot spots," tended to live in significantly more deprived areas with worse housing characteristics, had a lower socioeconomic status, had lower levels of health insurance, and worse access to early detection and diagnosis.

In addition, patients living in rural areas showed small, but statistically significant, at diagnosis compared with those living in urban areas.