Breast Cancer

What is breast self-examination (BSE)?

All women should be trained in breast self-examination (BSE). Women should be strongly encouraged to examine their breasts monthly. The minimum benefit of this practice is the greater likelihood of detecting a mass at a smaller size when it can be treated with ore limited surgery.

Who should receive genetic counseling for breast cancer?

All women with strong family histories for breast cancer should be referred to genetic screening programs whenever possible, particularly women of Ashkenazi Jewish descent who have a high likelihood of a specific BRCA-1 mutation (deletion of adenine and guanine at position 185).

What are BRCA mutations?

Although most breast cancers are sporadic, germline pathogenic variants in breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2 [BRCA]) and other genes account for a small percentage of breast cancers. -Not more than 10% of human breast cancers can be linked directly to germline mutations. Breast cancer susceptibility gene 1 and 2 (BRCA1 and BRCA2 [BRCA]) mutation carriers have increased risks of developing a second breast cancer. Therefore, even though breast conservation therapy is effective in these patients, they may opt to undergo bilateral mastectomy to reduce their risk of a second breast cancer.

What is BRCA-1?

Another tumor suppressor gene, BRCA-1, has been identified at the chromosomal locus 17q21; this gene encodes a zinc finger protein, and the product therefore may function as a transcriptional factor. The gene appears to be involved in gene repair. Women who inherit a mutated allele of this gene from either parent have at least a 60-80% lifetime chance of developing breast cancer and about a 33% chance of developing ovarian cancer. Men who carry a mutant allele of the gene have an increased incidence of prostate cancer and breast cancer.

What is BRCA-2?

BRCA-2 has been localized to chromosome 13q12 and is associated with an increased incidence of breast cancer in men and women.

What is the appropriate treatment for metastatic disease?

Because the diagnosis of metastatic disease alters the outlook for the patient so drastically, it should not be made without biopsy. Because therapy of systemic disease is palliative, the potential toxicities of therapies should be balanced against the response rates. The presence of estrogen and progesterone receptors is a strong indication for endocrine therapy. -Because of their lack of toxicity and because some patients whose receptor analyses are reported as negative respond to endocrine therapy, an endocrine treatment should be attempted in virtually every patient with metastatic breast cancer. -In most patients, the initial endocrine therapy should now be an aromatase inhibitor rather than tamoxifen. Radiation therapy and occasionally surgery are effective at relieving the symptoms of metastatic disease, particularly when bony sites are involved. Most patients with metastatic disease and certainly all who have bone involvement should receive concurrent bisphosphanates.

What is male breast cancer?

Breast cancer is about 1/150th as frequent in men as in women. It usually presents as a unilateral lump in the breast and is frequently not diagnosed promptly. Given the small amount of soft tissue and the unexpected nature of the problem, locally advanced presentations are somewhat more common. Any unilateral mass in a man over the age of 40 should receive a careful workup all the way through biopsy. -The risk of cancer is much greater in men with gynecomastia. Male breast cancer is best managed by mastectomy and axillary lymph node dissection (modified radical mastectomy). Patients with locally advanced disease or positive nodes should also be treated with irradiation.

How is breast cancer staged?

Breast cancer is staged using the American Joint Committee on Cancer and the International Union for Cancer Control classification system for Tumor, Nodes, and Metastases (TNM). In the TNM system, patients are assigned a clinical stage (cTNM) preoperatively. Following surgery, the pathologic stage (pTNM) is then determined.

What is the epidemiology of breast cancer?

Breast cancer is the second most commonly diagnosed cancer worldwide, including low- and middle-income countries. The incidence rates are highest in North America, Australia/New Zealand, and in western and northern Europe and lowest in Asia and sub-Saharan Africa. Breast cancer mortality rates have been decreasing since the 1970s. This decrease in mortality is due to improved breast cancer screening and improvements in adjuvant therapy.

What is the recommended screening for breast cancer?

Breast cancer is virtually unique among the epithelial tumors in adults in that screening (in the form of annual mammography) has been proven to improve survival. It seems prudent to recommend annual mammography for women past the age of 40.

How is a proper breast examination performed?

Breast examination by the physician should be performed in good light so as to see retractions and other skin changes. The nipple and areolae should be inspected, and an attempt should be made to elicit nipple discharge. All regional lymph node groups should be examined, any any lesions should be measured. In pre-menopausal women, lesions that are either equivocal or non-suspicious on physical examination should be re-examined in 2-4 weeks, during the follicular phase of the menstrual cycle. Days 5-7 of the cycle are the best time for breast examination.

What is breast-conserving therapy (BCT)?

Breast-conserving therapy (BCT) is comprised of breast-conserving surgery (BCS; ie, lumpectomy) plus RT. The goals of BCT are to provide the survival equivalent of mastectomy, a cosmetically acceptable breast, and a low rate of recurrence in the treated breast.

What is the post-treatment surveillance for breast cancer patients?

Cancer survivors who have completed treatment for breast cancer should undergo regular follow-up. Annual mammography should also be performed in patients who underwent breast-conserving therapy.

What are "classic" mammographic findings of breast cancer?

Classic mammographic findings of breast cancer include the presence of a soft tissue mass or density and grouped microcalcifications. The most specific feature is a spiculated, high-density mass, with nearly 90 percent representing an invasive cancer. Sonographic features of malignancy include hypoechogenicity; internal calcifications; shadowing; a lesion taller than it is wide; and spiculated, indistinct, or angular margins.

What special considerations can be made for fertility preservation?

Clinicians should discuss with patients the risk of infertility and possible interventions to preserve fertility prior to initiating potentially gonadotoxic therapy. This discussion should occur soon after diagnosis, since some interventions to preserve fertility take time and could delay the start of treatment.

What are contraindications for BCT?

Criteria that preclude BCT include: ●Multicentric disease ●Large tumor size in relation to breast ●Presence of diffuse malignant-appearing calcifications on imaging (ie, mammogram or magnetic resonance imaging [MRI]) ●Prior history of chest RT (eg, mantle radiation for Hodgkin disease) ●Pregnancy ●Persistently positive margins despite attempts at re-excision

What differential diagnoses should be considered when evaluating a patient for breast cancer?

Ductal carcinoma in situ (DCIS) represents a heterogeneous group of precancerous lesions confined to the breast ducts and lobules and is potentially a precursor lesion to invasive breast cancer. Microinvasive breast cancer (or DCIS with microinvasion) typically presents as a palpable mass. Other cancers: -Breast sarcoma -Paget disease: Paget disease of the breast typically presents as a raw, scaly, vesicular, or ulcerated lesion that begins on the nipple and spreads to the areola. -Phyllodes tumors -Lymphoma

What are breast masses in pregnant/lactating women?

During pregnancy, the breast grows under the influence of estrogen, progesterone, prolactin, and human placental lactogen. Lactation is suppressed by progesterone, which blocks the effects of prolactin. After delivery, lactation is promoted by the fall in progesterone levels, which leaves the effects of prolactin unopposed. The development of a dominant mass during pregnancy or lactation should never be attributed to hormonal changes, and biopsy should never be performed under local anesthesia. Pregnant women often have more advanced disease because the significance of a breast mass was not fully considered.

What are ER and PR?

Estrogen receptor (ER) and progesterone receptor (PR) are prognostic factors for invasive breast cancer, particularly in the first five years following initial diagnosis. In addition, patients who are ER and/or PR positive are candidates for endocrine therapy as neoadjuvant or adjuvant treatment. ER-positivity is defined by immunohistochemistry (IHC) for ER and PR in more than 1 percent of tumor cells.

What is the anatomy of the female breast?

Fibrous and fatty tissue and 15-20 lobes in each breast. 80% of breast is fat during reproductive years. Lobes are further divided into lobules containing alveoli of secretory cells with ducts that conduct to a reservoir under the nipple.

When is further imaging indicated for patients diagnosed with breast cancer?

For patients with localized bone pain or an elevated alkaline phosphatase, we obtain a bone scan. If the bone scan is negative and clinical suspicion warrants further evaluation, magnetic resonance imaging (MRI) should be performed localized to the symptomatic area. For patients with abnormal liver function tests, an elevated alkaline phosphatase, abdominal pain, or an abnormal abdominal or pelvic examination, we obtain a computed tomography (CT) scan of the abdomen and pelvis. Abdominal MRI or ultrasound would be reasonable alternatives depending on the specific symptom to be evaluated. Positron emission tomography-CT (PET-CT) would be reasonable if whole-body screening for metastatic disease is also desired. For patients presenting with pulmonary complaints (ie, cough or hemoptysis), we obtain a chest CT scan, although chest radiograph would be a reasonable alternative. For patients with stage IIIA or higher disease, regardless of whether symptoms are present or not, we obtain a whole-body PET-CT or, alternatively, a bone scan as well as a CT scan of the chest, abdomen, and pelvis. Patients with inflammatory breast cancer, regardless of stage, should also undergo imaging evaluation.

What special considerations can be made for older female patients with breast cancer?

For some patients with estrogen receptor-positive breast cancer, in whom surgery is not an option or life expectancy is limited, primary hormonal treatment with either tamoxifen or an aromatase inhibitor without surgery or radiation therapy can be used.

What are the most common receptor subtypes of breast cancer?

Hormone receptor (ER and/or PR) positive cancers comprised the majority of cases.

What is HER2?

Human epidermal growth factor receptor 2 (HER2) overexpression is present in 20 percent of patients and predicts those who will benefit from HER2-directed therapy. HER2 overexpression is detected by uniform intense membrane staining of >30 percent of invasive tumor cells (IHC 3+) or the presence of HER2 gene amplification by fluorescence in situ hybridization defined as a ratio of HER2/CEP17 (centromeric probe to chromosome 17) ratio ≥2.0.

What is a breast cyst?

If non-bloody fluid is aspirated and the lesion is thereby cured, the diagnosis (cyst) and therapy have been accomplished together.

What are other risk factors for breast cancer development?

In addition to the other factors, radiation may be a risk factor in younger women. Women who have been exposed before age 30 to radiation have a substantial increase in risk of breast cancer, whereas radiation exposure after age 30 appears to have a minimal carcinogenic effect on the breast.

How does breast cancer often present clinically?

In countries with established breast cancer screening programs, most patients present due to an abnormal mammogram. However, up to 15 percent of women are diagnosed with breast cancer due to the presence of a breast mass that is not detected on mammogram (mammographically occult disease), and another 30 percent present with a breast mass in the interval between mammograms (interval cancers).

What is the treatment for early stage breast cancer (stages I, IIA and some IIB)?

In general, patients with early-stage breast cancer undergo primary surgery (lumpectomy or mastectomy) to the breast and regional nodes with or without radiation therapy (RT). Following definitive local treatment, adjuvant systemic therapy may be offered based on primary tumor characteristics, such as tumor size, grade, number of involved lymph nodes, the status of estrogen (ER) and progesterone (PR) receptors, and expression of the human epidermal growth factor 2 (HER2) receptor. However, some patients with early-stage breast cancer (particularly those with HER2-positive or triple-negative disease) may be treated with neoadjuvant therapy first, followed by surgery.

What is the most common kind of invasive breast cancer?

Infiltrating ductal carcinomas are the most common type of invasive breast cancer, accounting for 70 to 80 percent of invasive lesions. These lesions are characterized by cords and nests of cells with varying amounts of gland formation and cytologic features that range from bland to highly malignant.

What are infiltrating lobular carcinomas?

Infiltrating lobular carcinomas comprise about 8 percent of invasive breast cancers. Microscopically, they are characterized by small cells that insidiously infiltrate the mammary stroma and adipose tissue individually and in a single-file pattern.

What is the metastasis (M) component of breast cancer staging?

M followed by a 0 or 1 indicates whether the cancer has spread to distant organs -- for example, the lungs, liver, or bones. MX: Distant spread (metastasis) cannot be assessed. M0: No distant spread is found on x-rays (or other imaging tests) or by physical exam. M1: Cancer has spread to distant organs (most often to the bones, lungs, brain, or liver).

What are benign breast masses?

Only about 1 in every 5 to 10 breast biopsies leads to a diagnosis of cancer. The vast majority of benign breast masses are due to "fibrocystic" disease, a descriptive term for small fluid-filled cysts and modest epithelial cell and fibrous tissue hyperplasia. However, fibrocystic disease is a histologic, not a clinical, diagnosis.

What is the role of radiation therapy for early stage breast cancer?

Postmastectomy radiation therapy (RT) is indicated for patients at high risk for local recurrence, such as those with cancer involving the deep margins and pathologically involved axillary lymph nodes.

What is ductal carcinoma in situ (DCIS)?

Proliferation of cytologically malignant breast epithelial cells within the ducts is termed DCIS. At least one-third of the cases of untreated DCIS progress to invasive breast cancer within 5 years. For many years, the standard treatment for this disease was mastectomy. However, since treatment of this condition by lumpectomy and radiation therapy gives survival that is as good as the survival for invasive breast cancer by mastectomy, it appears paradoxical to recommend more aggressive therapy for a "less" malignant disease.

What is lobular neoplasia?

Proliferation of cytologically malignant cells within the lobules is termed lobular neoplasia. Nearly 30% of patients who have had adequate local excision of the lesion develop breast cancer (usually infiltrating ductal cell carcinoma) over the next 15-20 years. Ipsilateral and contralateral disease are equally common. Therefore, lobular neoplasia may be a pre-malignant lesion that suggests an elevated risk of subsequent breast cancer, rather than a form of malignancy itself, and aggressive local management seems unreasonable. Most patients should be treated with tamoxifen for 5 years and followed with careful annual mammography and semi-annual physical examinations.

What are signs of metastatic disease?

Symptoms of metastatic breast cancer depend on the organs involved, with the most common sites of involvement being the bone (eg, back or leg pain), liver (abdominal pain, nausea, jaundice), and lungs (eg, shortness of breath or cough).

What is the role of adjuvant therapy in treatment of early stage breast cancer (stage I, IIA and some IIB)?

Systemic therapy refers to the medical treatment of breast cancer using endocrine therapy, chemotherapy, and/or biologic therapy. Patients with hormone receptor-positive breast cancer should receive endocrine therapy. For patients with ER/PR and HER2-negative disease (triple-negative breast cancer), we prefer to administer adjuvant chemotherapy if the tumor size is ≥0.5 cm.

What is the tumor (T) component of breast cancer staging?

T followed by a number from 0 to 4 describes the main (primary) tumor's size and if it has spread to the skin or to the chest wall under the breast. Higher T numbers mean a larger tumor and/or wider spread to tissues near the breast. TX: Primary tumor cannot be assessed. T0: No evidence of primary tumor. Tis: Carcinoma in situ (DCIS, or Paget disease of the breast with no associated tumor mass) T1 (includes T1a, T1b, and T1c): Tumor is 2 cm (3/4 of an inch) or less across. T2: Tumor is more than 2 cm but not more than 5 cm (2 inches) across. T3: Tumor is more than 5 cm across. T4 (includes T4a, T4b, T4c, and T4d): Tumor of any size growing into the chest wall or skin. This includes inflammatory breast cancer.

What is the classic "breast mass"?

The "classic" characteristics of a cancerous lesion include a hard, immovable, single dominant lesion with irregular borders. However, these features cannot reliably distinguish a benign from a malignant tumor.

What is the Li-Fraumeni syndrome?

The Li-Fraumeni syndrome is characterized by inherited mutations in the p53 tumor suppressor gene, which lead to an increased incidence of breast cancer, osteogenic sarcomas, and other malignancies.

What is the appropriate treatment for metastatic disease (cont.)?

Unlike many other epithelial malignancies, breast cancer responds to several chemotherapeutic agents, including anthracyclines, alkylating agents, taxanes and antimetabolites.

What steps should be taken if a suspicious mass is detected on physical examination?

A dominant mass in a post-menopausal woman or a dominant mass that persists through a menstrual cycle in a pre-menopausal woman should be aspirated by fine-needle biopsy or referred to a surgeon. Solid lesions that are persistent, recurrent, complex or bloody cysts require mammography and biopsy. -Ultrasound can be used in place of fine-needle aspiration to distinguish cysts from solid lesions.

What is a mastectomy?

A mastectomy is indicated for patients who are not candidates for BCT and those who prefer mastectomy.

What is mixed ductal/lobular carcinoma?

A mixed histologic appearance comprising both ductal and lobular characteristics is defined as a mixed invasive carcinoma. These comprise 7 percent of invasive breast cancers.

What is the treatment for locally advanced breast cancer (some stage IIB disease, IIIA and IIIC)?

Locally advanced breast cancer is best managed with multimodality therapy employing systemic and locoregional therapy. More than 90% of patients with locally advanced breast cancer show a partial or better response to multi-drug chemotherapy regimens that include an anthracycline.

What are the molecular subtypes of breast cancer?

Luminal subtypes — The luminal subtypes are characterized as luminal A and luminal B. They are the most common subtypes of breast cancer and make up the majority of estrogen (ER)-positive breast cancers. HER2-enriched — The human epidermal growth factor receptor 2 (HER2)-enriched subtype makes up about 10 to 15 percent of breast cancers and is characterized by high expression of HER2 and proliferation gene clusters and low expression of the luminal and basal gene clusters. These tumors are often negative for ER and progesterone (PR). Basal subtypes — Most of these tumors fall under the category of triple-negative breast cancers because they are ER, PR, and HER2 negative.

How is the extent of breast disease assessed?

Mammographic assessment of the extent of ductal carcinoma in situ (DCIS) and early invasive carcinoma begins during diagnostic mammography and continues through the biopsy, specimen management, and the postexcision mammogram. -A significant limitation of mammographic assessment of disease extent is the obscuring of the borders or extent of the primary tumor by dense overlying tissue. Dense breasts can limit the sensitivity of mammography both for detection of breast cancers and for delineating disease extent.

What is neoadjuvant systemic therapy?

Most patients with locally advanced breast cancer, and some with earlier-stage disease (particularly if triple negative or human epidermal growth factor receptor 2 [HER2] positive), are treated with neoadjuvant systemic therapy. The goal of treatment is to induce a tumor response before surgery and enable breast conservation. All patients should undergo surgery following neoadjuvant systemic therapy, even if they have a complete clinical and/or radiological response.

What is the lymph node (N) component of breast cancer staging?

N followed by a number from 0 to 3 indicates whether the cancer has spread to lymph nodes near the breast and, if so, how many lymph nodes are involved. NX: Nearby lymph nodes cannot be assessed (for example, if they were removed previously). N0: Cancer has not spread to nearby lymph nodes. N1: Cancer has spread to 1 to 3 axillary (underarm) lymph node(s), and/or tiny amounts of cancer are found in internal mammary lymph nodes (those near the breast bone) on sentinel lymph node biopsy. N2: Cancer has spread to 4 to 9 lymph nodes under the arm, or cancer has enlarged the internal mammary lymph nodes. N3: Any of the following: -Cancer has spread to 10 or more axillary lymph nodes, with at least one area of cancer spread greater than 2 mm, OR Cancer has spread to the lymph nodes under the collarbone (infraclavicular nodes), with at least one area of cancer spread greater than 2 mm.

What is breast cancer receptor testing?

Newly diagnosed breast cancers must be tested for estrogen (ER) and progesterone (PR) receptor expression and for overexpression of human epidermal growth factor 2 (HER2) receptors. This information is critical for both prognostic and therapeutic purposes.

How is non-metastatic breast cancer categorized?

Nonmetastatic breast cancer is broadly considered in two categories: Early stage - This includes patients with stage I, IIA, or a subset of stage IIB disease (T2N1). Locally advanced - This includes a subset of patients with stage IIB disease (T3N0) and patients with stage IIIA to IIIC disease.

How is breast cancer diagnosed?

The diagnosis of breast cancer is defined by the presence of malignant epithelial cells (carcinoma). Doctors often use additional tests to find or diagnose breast cancer. They may refer women to a breast specialist or a surgeon. This does not mean that she has cancer or that she needs surgery. These doctors are experts in diagnosing breast problems. Breast ultrasound. A machine that uses sound waves to make detailed pictures, called sonograms, of areas inside the breast. Diagnostic mammogram. If you have a problem in your breast, such as lumps, or if an area of the breast looks abnormal on a screening mammogram, doctors may have you get a diagnostic mammogram. This is a more detailed X-ray of the breast. Magnetic resonance imaging (MRI). A kind of body scan that uses a magnet linked to a computer. The MRI scan will make detailed pictures of areas inside the breast. Biopsy. This is a test that removes tissue or fluid from the breast to be looked at under a microscope and do more testing. There are different kinds of biopsies (for example, fine-needle aspiration, core biopsy, or open biopsy)

What is the female to male ratio for breast cancer?

The female to male ratio is about 150:1.

What is the prognosis for patients with breast cancer?

The majority of breast cancer recurrences occur within the first five years of diagnosis, particularly with hormone receptor-negative disease.

What is the role of oral contraceptives in breast cancer risk?

The most credible meta-analyses of oral contraceptive use suggest that these agents cause little if any increased risk of breast cancer. By contrast, oral contraceptives offer a substantial protective effect against ovarian epithelial tumors and endometrial cancers.

What are prognostic variables for early stage breast cancer?

The most important prognostic variables are provided by tumor staging. The size of the tumor and the status of the axillary lymph nodes provide reasonably accurate information on the likelihood of tumor relapse. Estrogen and progesterone receptor status are of prognostic significance. Tumors that lack either or both of these receptors are more likely to recur than tumors that have them. Molecular changes in the tumor are also useful. Tumors that over-express HER-2 or have a mutated p53 gene have a worse prognosis.

What are signs of locally advanced disease?

The signs of more advanced locoregional disease include axillary adenopathy (suggesting locoregional disease) or skin findings such as erythema, thickening, or dimpling of the overlying skin (peau d'orange), suggesting inflammatory breast cancer.

What dates in a woman's life have a major impact on breast cancer?

The three dates in a woman's life that have a major impact on breast cancer incidence are age at menarche, age at first full-term pregnancy, and age at menopause. -Women who experience menarche at age 16 have only 50-60% of the breast cancer risk of a woman having menarche at age 12; the lower risk persists throughout life. -Menopause occurring 10 years before the median age of menopause (52 years), whether naturally or surgically induced, reduces lifetime bresat cancer risk by about 35%. -Women who have a first full-term pregnancy by age 18 have a 30-40% lower risk of breast cancer compared with nulliparous women. Thus, length of menstrual life--particularly the fraction occurring before first full-term pregnancy--is a substantial component of the total risk of breast cancer. These three factors can account for 70-80% of the variation in breast cancer frequency in different countries.