AUTHOR: Bharti Rathore, MD
Breast cancer refers to epithelial carcinoma arising from the ducts (ductal) or the lobules (lobular) of the breast that is initially in situ but can progress to become invasive in nature.
Carcinomas make up the majority of breast malignancies and originate in the epithelium of the collecting ducts (ductal) or the terminal lobular ducts (lobular). Sarcomas are rare, constituting less than 1% of primary breast cancers, and arise from stromal or connective tissue. Tumor grade is based on tubule formation, nuclear pleomorphism, and mitotic counts using the Nottingham score to determine low, intermediate, or high grade. Higher grade is associated with a poorer long-term prognosis.
Initially, breast carcinoma may be divided into invasive and in situ lesions (Table 1). Invasive ductal carcinoma accounts for the majority, approximately 80%, of invasive carcinomas. Invasive lobular carcinomas constitute approximately 10% to 15% of cases. Other subtypes include mucinous, tubular, medullary, micropapillary, and papillary. Both in situ and invasive carcinomas are often found in the same quadrant of the breast. Additionally, multifocal carcinomas are not uncommon, and bilateral breast carcinomas occur in 1% to 2% of newly diagnosed cases.
TABLE 1 Simplified Classification of Breast Carcinoma Based on Histology
Type of Carcinoma | Percentage of All Cases Diagnosed | ||
---|---|---|---|
Ductal carcinoma | |||
In situ | 5 | ||
Infiltrating | 70 | ||
Infiltrating with uniform histologic appearance | 10 | ||
Medullary, colloid, comedo, tubular, papillary | |||
Lobular carcinoma | |||
In situ | 3 | ||
Infiltrating | 9 | ||
Inflammatory carcinoma | 2 | ||
Paget disease | 1 |
From Gershenson DM et al: Comprehensive gynecology, ed 8, Philadelphia, 2022, Elsevier.
Historically, the treatment of breast cancer was based on tumor histologic characteristics, axillary node status, tumor size, receptor patterns, and grade of differentiation. In addition to simplified histologic classification, a classification based on gene expression or profiling, including the presence of hormone receptors, has evolved. Identification of tumor receptor status is critical because endocrine therapy is used both for adjuvant therapy and in the management of advanced disease. The genomic analysis of tumors has led to the molecular subtyping of breast cancers. In the early 2000s, breast tumors were classified into four different molecular subtypes: luminal, basal, HER2, and normal. Subsequently, the luminal group was further differentiated into luminal-A and luminal-B subgroups. Basal-like tumors include triple-negative tumors, tumors that are estrogen, progesterone, and HER2 negative by immunohistochemistry. A more aggressive subtype of triple-negative tumors, claudin-low tumors, has also been described. These divisions are detailed in Table 2.
TABLE 2 Classification of Breast Carcinoma Based on Gene Profiling and Hormone Receptor
Expression Type | Grade | Characteristic Behavior | Hormone Receptor Status∗ |
---|---|---|---|
Luminal A | Usually low grade | Good prognosis | E and P+ |
Luminal B | All grades | Mixed prognosis | E and P+, Her2 (Neu)+ |
Her2 (Neu) | Higher grades | Poor prognosis | E and P-, Her2 (Neu)+ |
Basal | Usually grade 3 | Poor prognosis | Triple negative |
Normal breast | Usually low grade | Good prognosis | Triple negative |
∗E, Estrogen receptor; P, progesterone receptor.
Normal breast does not express gene profiling of basal elements and myoepithelial gene expression.
From Gershenson DM et al: Comprehensive gynecology, ed 8, Philadelphia, 2022, Elsevier.
|
TABLE 5 Known Genetic Mutations in Breast Cancer and Their Management
Genetic Mutation | Breast Cancer Risk | Management |
---|---|---|
ATM | Increased by 15%-40% | Annual mammography starting at age 40 with consideration for breast tomosynthesis/magnetic resonance imaging (MRI) |
BARD1 | Limited evidence for increased risk but stronger for triple-negative breast cancer | Annual mammography starting at age 40 with consideration for breast tomosynthesis/MRI |
BRCA1 BRCA2 | Both carry increased absolute risk greater than 60% | Breast awareness starting at age 18 Clinical breast examination every 6-12 mo starting at age 25 yr Breast screening: Age 25-29 yr: Annual breast MRI screening with contrast or mammogram with consideration of tomosynthesis, only if MRI is unavailable or individualized based on family history if a breast cancer diagnosis before age 30 is present Age 30-75 yr: Annual mammogram with consideration of tomosynthesis and breast MRI screening with contrast Age >75 yr: Management should be individualized Consider risk-reducing mastectomy |
BRIP1 | Potential increase in risk | Management based on family history |
CDH1 | Increased absolute risk 41%-60% | Annual mammogram with consideration of tomosynthesis or breast MRI with contrast starting at age 30 |
CHECK2 | Increased absolute risk 15%-40% | Annual mammography starting at age 40 with consideration for breast tomosynthesis/MRI |
MSH2 MLH1 MSH6 PMS2 EPCAM | Limited evidence of increased risk, absolute risk is <15% | Management based on family history |
NBN | Increased risk of breast cancer with variant 657del5 | Management based on family history |
NF1 | Increased absolute risk 15%-40% | Annual mammography starting at age 30 with consideration for breast tomosynthesis/MRI |
PALB2 | Increased absolute risk 41%-60% | Annual mammography starting at age 30 with consideration for breast tomosynthesis/MRI Consider risk-reducing mastectomy |
PTEN | Increased absolute risk 40%-60% | Breast awareness starting at age 18 Clinical breast examination every 6-12 mo starting at age 25 yr (or 5-10 yr before earliest known breast cancer in the family) Breast screening: Age 25-29 yr: Annual breast MRI screening with contrast or mammogram with consideration of tomosynthesis, only if MRI is unavailable or individualized based on family history if a breast cancer diagnosis before age 30 is present Age 30-75 yr: Annual mammogram with consideration of tomosynthesis and breast MRI screening with contrast Age >75 yr: Management should be individualized Consider risk-reducing mastectomy |
RAD51C | Increased absolute risk 15%-40% | Management based on family history |
RAD51D | Increased absolute risk 15%-40% | Management based on family history |
STK11 | Increased absolute risk 40%-60% | Annual mammography alternating with breast MRI every 6 mo starting at age 30 and clinical breast examination every 6 mo |
TP53 | Increased absolute risk >60% | Breast awareness starting at age 18 Clinical breast examination every 6-12 mo starting at age 20 yr Breast screening: Age 20-29 yr: Annual breast MRI screening with contrast or mammogram with consideration of tomosynthesis, only if MRI is unavailable or individualized based on family history if a breast cancer diagnosis before age 30 is present Age 30-75 yr: Annual mammogram with consideration of tomosynthesis and breast MRI screening with contrast Age >75 yr: Management should be individualized Consider risk-reducing mastectomy |
From Gershenson DM et al: Comprehensive gynecology, ed 8, Philadelphia, 2022, Elsevier.
TABLE 6 Major Inherited Gene Mutation Syndromes Associated With Breast Cancer
Syndrome | Gene | Incidence | Lifetime Breast Cancer Risk | Associated Cancer Risks |
---|---|---|---|---|
BRCA1 | BRCA1 | 1/500-1/1000 | 85% | Ovary and pancreas |
BRCA2 | BRCA2 | Unclear | 85% | Ovary and pancreas |
Cowden | PTEN | 1/100,000-1/200,000 | 50% | Thyroid and endometrium |
Li-Fraumeni | TP53 | 1/20,000 | 90% | Sarcoma, brain, and leukemia |
Other syndromes, including Peutz-Jeghers syndrome, ataxia telangiectasia, CHEK2 gene mutation, and Fanconi syndrome, have much smaller lifetime risks with poorer penetrance.
From Gershenson DM et al: Comprehensive gynecology, ed 8, Philadelphia, 2022, Elsevier.
TABLE 4 Factors Associated With a Decreased Risk for Breast Cancer
Demographic | Qualification | Relative Risk |
---|---|---|
Born and living outside Western countries | ||
Late menarche | After age 14 | |
Oophorectomy | Yes vs. no | 0.3 |
Lactation | >16 mo vs. none | 0.73 |
Parity | ≥5 vs. 0 | 0.73 |
Postmenopausal body mass (kg/m2) | <22.9 vs. >30.7 | 0.63 |
Physical activity | Yes vs. no | 0.70 |
Vitamin D | Low levels associated with risk | |
Intake of vitamin D | Associated with decreased risk | |
Olive oil and omega-3 fatty acids | ||
Low-fat diet | Results suggestive but not yet conclusive | |
Aspirin | >1×/wk for ≥16 mo vs. no use | 0.79 |
From Gershenson DM et al: Comprehensive gynecology, ed 8, Philadelphia, 2022, Elsevier.
TABLE 3 Risk Factors for Breast Cancer
Risk Factor | Qualification | Relative Risk |
---|---|---|
Age | ≤49 yr 50-59 yr Age 60-69 yr ≥70 yr | 2.0 2.3 3.5 6.7 |
Geographic | Common in Western countries | |
Age at menarche | >14 yr (low risk) vs. <12 yr | 1.5 |
Age at first full-term pregnancy | <20 yr (low risk) vs. >30 yr | 1.9-3.5 |
Late menopause | <45 yr (low risk) vs. >55 yr (high risk) | 2.0 |
Hormone replacement therapy | No use vs. current | 1.2 |
Contraceptive pill use | None vs. past or current use | 1.07-1.2 |
Alcohol use | None vs. 2-5 drinks/day | 1.4 |
Postmenopausal weight gain | Women with a higher body mass index (BMI) | 1.1 per 5 BMI units |
Bone density | Lowest vs. highest quartile | 2.7-3.5 |
Nightshift work | Exposed to nightshift work | 1.48 |
Smoking | History of smoking | 1.10∗ |
Benign breast disease | None vs. positive biopsy result | 1.7 |
Breast density (as measured by mammography) | 0% vs. ≥75% | 1.8-6.0 |
Hyperplasia with atypia | None vs. positive biopsy result | 3.7 |
Multiple relatives, not first degree, with breast cancer | ||
One first-degree relative with breast cancer (mother or sister) | None vs. yes | 2.6 |
Two or more first-degree relatives | Increased risk if the cancers are premenopausal | |
Deleterious BRCA1/BRCA2 genes | Negative vs. positive | 2.0-7.0 |
Mantle radiation for treatment of malignancy | Very high risk, which increases with age |
From Gershenson DM et al: Comprehensive gynecology, ed 8, Philadelphia, 2022, Elsevier.
Benign disease is summarized in Table 7. Noninvasive neoplasms of the breast were previously broadly divided into two major types, LCIS and DCIS (Box 1). LCIS is no longer regarded as a neoplasm of the breast in the eighth edition of the AJCC staging system but is regarded as a risk factor for the development of breast cancer.
BOX 1 Transverse Rectus Abdominis Muscle Flap Reconstruction
From Townsend CM et al: Sabiston textbook of surgery, ed 21, St Louis, 2022, Elsevier.
TABLE 7 American Board of Pathology Histologic Classification of Benign Disease
Histopathologic Findings | Approximate Relative Risk | ||
---|---|---|---|
Nonproliferative | No added risk | ||
Cysts | |||
Duct ectasia | |||
Calcification | |||
Fibroadenoma | |||
Milk ductal epithelial hyperplasia | |||
Sclerosing adenosis | No added risk | ||
Papillomatosis | Slight added risk | ||
Radial scars | |||
Complex sclerosing lesions | ? | ||
Moderate florid hyperplasia | 1.5:1-2:1 | ||
Atypical hyperplasia (ductal and lobular) | 4:1 | ||
Extensive ductal involvement of atypical hyperplasia | 7:1 | ||
Lobular carcinoma in situ | 10:1 | ||
Ductal carcinoma in situ | 10:1 |
From Niederhuber JE: Abeloffs clinical oncology, ed 6, Philadelphia, 2020, Elsevier.
The following nonmalignant breast lesions can simulate breast cancer on both physical and mammogram examinations:
BOX 3 Indications for Stereotactic Core Biopsy
From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.
BOX 4 Contraindications to Stereotactic Core Biopsy
From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.
Figure 1 A 42-yr-old woman with BRCA2 mutation.
Magnetic resonance imaging (MRI) screening showed a 1.2-cm invasive ductal cancer in the lower outer left breast seen only on MRI (A and B) and subsequently on second-look ultrasound. C, The mammogram showed only dense breast tissue.
From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.
TABLE 8 Guidelines for Evaluation and Treatment of Nonpalpable Ductal Carcinoma In Situ
DCIS, Ductal carcinoma in situ.
From Niederhuber JE: Abeloffs clinical oncology, ed 6, Philadelphia, 2020, Elsevier.
BOX 2 American Cancer Society MRI Breast Cancer Screening Recommendations
From Townsend CM et al: Sabiston textbook of surgery, ed 21, St Louis, 2022, Elsevier.
Table 9 describes the pathologic staging of breast cancer.
TABLE 9 Pathologic Staging of Breast Cancer
TX | Primary Tumor Cannot Be Assessed | ||
---|---|---|---|
T0 | No evidence of primary tumor | ||
Tis | Carcinoma in situ | ||
Tis (DCIS) | Ductal carcinoma in situ | ||
Tis (LCIS) | Lobular carcinoma in situ | ||
Tis (Paget) | Paget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS and/or LCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted | ||
T1 | Tumor ≤20 mm in greatest dimension | ||
T1mi | Tumor ≤1 mm in greatest dimension | ||
T1a | Tumor >1 mm but ≤5 mm in greatest dimension | ||
T1b | Tumor >5 mm but ≤10 mm in greatest dimension | ||
T1c | Tumor >10 mm but ≤20 mm in greatest dimension | ||
T2 | Tumor >20 mm but ≤50 mm in greatest dimension | ||
T3 | Tumor >50 mm in greatest dimension | ||
T4 | Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) | ||
T4a | Extension to chest wall, not including only pectoralis muscle adherence/invasion | ||
T4b | Ulceration and/or ipsilateral satellite nodules and/or edema (including peau dorange) of the skin, which do not meet the criteria for inflammatory carcinoma | ||
T4c | Both T4a and T4b | ||
T4d | Inflammatory carcinoma | ||
NX | Regional lymph nodes cannot be assessed (e.g., previously removed) | ||
N0 | No regional lymph node metastasis | ||
N1 | Metastasis to movable ipsilateral level I, II axillary lymph node(s) | ||
N2 | Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted or in clinically detected ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis | ||
N2a | Metastases in ipsilateral level I, II axillary lymph nodes fixed to one another (matted) or to other structures | ||
N2b | Metastases only in clinically detected ipsilateral internal mammary nodes and in the absence of clinically evident level I, II axillary lymph node metastases | ||
N3 | Metastases in ipsilateral infraclavicular (level III axillary) lymph node(s), with or without level I, II axillary node involvement, or in clinically detected ipsilateral internal mammary lymph node(s) and in the presence of clinically evident level I, II axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph node(s), with or without axillary or internal mammary lymph node involvement | ||
N3a | Metastasis in ipsilateral infraclavicular lymph node(s) | ||
N3b | Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) | ||
N3c | Metastasis in ipsilateral supraclavicular lymph node(s) | ||
M0 | No clinical or radiographic evidence of distant metastasis | ||
cM0(i+) | No clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases | ||
M1 | Distant detectable metastases as determined by classic clinical and radiographic means and/or histologically proven >0.2 mm | ||
GX | Grade cannot be assessed | ||
G1 | Low combined histologic grade (favorable) | ||
G2 | Intermediate combined histologic grade (moderately favorable) | ||
G3 | High combined histologic grade (unfavorable) |
Stage Groupings in Breast Cancer | |||
---|---|---|---|
Stage | T | N | M |
0 | Tis | N0 | M0 |
IA | T1 | N0 | M0 |
IB | T0-T1 | N1mi | M0 |
IIA | T0-T1 | N1 | M0 |
T2 | N0 | M0 | |
IIB | T2 | N1 | M0 |
T3 | N0 | M0 | |
IIIA | T0-T2 | N2 | M0 |
T3 | N1-N2 | M0 | |
IIIB | T4 | N0-N2 | M0 |
IIIC | Any T | N3 | M0 |
IV | Any T | Any N | M1 |
From Goldman L, Schafer AI: Goldmans Cecil medicine, ed 24, Philadelphia, 2012, Saunders; AJCC 8th ed., 2018.
Mammograms (Fig. E2, Fig. E3): 30% to 50% of breast cancers are detected by screening mammograms as a spiculated mass, a mass with or without microcalcifications, or a cluster of microcalcifications. MRI is particularly useful in patients with breast implants and when there is a strong family history of breast cancer. MRI is better for assessing response to neoadjuvant chemotherapy and for identifying the primary tumor in patients presenting with axillary adenopathy.
Figure E2 Mammogram and ultrasound findings of breast disease.
A, A stellate mass in the breast. The combination of a density with spiculated borders and distortion of surrounding breast architecture suggests a malignancy. B, Clustered microcalcification. Fine, pleomorphic, and linear calcifications that cluster together suggest the diagnosis of ductal carcinoma in situ (DCIS). C, An ultrasound image of breast cancer. The mass is solid, containing internal echoes, and displaying an irregular border. Most malignant lesions are taller than they are wide.
From Townsend CM et al [eds]: Sabiston textbook of surgery, ed 17, Philadelphia, 2004, Saunders.
Figure E3 Digital mammography and workup of breast calcifications.
A, Craniocaudal (CC) view in a routine screening of a 43-yr-old woman. Digital mammography penetrates dense breast tissue better than film-screen mammography, clearly showing diffuse benign pattern of large and small calcifications throughout the breast. B, CC view in a routine screening of a 46-yr-old woman. Digital mammography shows two areas of very faint calcification in the outer breast that require further workup. C, Close-up view of B, showing the calcifications (arrows) to be variable in size and shape, which is worrisome for malignancy, particularly ductal carcinoma in situ. Such tiny calcifications in a background of dense breast stroma are easier to see on digital mammography than on film-screen mammography. Computer-assisted diagnosis programs also help the radiologist to locate even tiny groups of faint calcifications such as these. D, Mediolateral view in the same patient as in B, showing that the calcifications are in the lower breast. E, Image from stereo core biopsy procedure in the same patient as in B, showing the core needle immediately proximal to one of the groups of calcifications. Stereo core biopsy allows histologic sampling of tiny groups of calcifications, which can be very helpful in planning surgical approach. This interventional procedure can decrease the total number of surgeries that a patient must undergo to achieve definitive treatment. F, Radiograph of specimen from stereo core biopsy procedure on the same patient as in B, showing that there are several tiny calcifications (arrows) within some of the core samples. Pathologic analysis of the core biopsy revealed ductal carcinoma in situ, high grade, with comedo features.
From Skarin AT: Atlas of diagnostic oncology, ed 4, Philadelphia, 2010, Elsevier.
TABLE 16 Commonly Used Cytotoxic Chemotherapy and Anti-HER2 Therapy Drugs in Metastatic Breast Cancer
Cytotoxic Chemotherapy | |||
---|---|---|---|
Albumin-bound paclitaxel Capecitabine Cisplatin Carboplatin Docetaxel Doxorubicin Epirubicin Eribulin Gemcitabine Ixabepilone Vinorelbine | |||
Anti-HER2 Therapy | |||
Ado-trastuzumab emtansine Lapatinib Pertuzumab Trastuzumab |
HER2, Human epidermal growth factor receptor 2.
From Niederhuber JE: Abeloffs clinical oncology, ed 6, Philadelphia, 2020, Elsevier.
TABLE 15 Median Survival in Months of Patients With Metastatic Breast Cancer by Location of Metastases
Location | Survival (Months) | ||
---|---|---|---|
Liver (>30% replacement) | 3 | ||
Lung (lymphangitic) | 3 | ||
Lung (nodular) | 22 | ||
Skin | 27 | ||
Bones | 36+ |
From Townsend CM et al: Sabiston textbook of surgery, ed 21, St Louis, 2022, Elsevier.
TABLE 12 Decision-Making for Systemic Therapy
Stage | Systemic Therapy | Comments |
---|---|---|
I (<1 cm) | ||
Hormone receptor-positive | Endocrine therapy ± chemotherapy | Consider genomic testing |
Hormone receptor-negative | Consider chemotherapy | |
HER-2-positive | Strongly consider trastuzumab and chemotherapy | |
I (>1 cm) | ||
Hormone receptor-positive | Endocrine therapy ± chemotherapy | Consider genomic testing |
Hormone receptor-negative | Chemotherapy | |
HER-2-positive | Trastuzumab and chemotherapy | |
II (Lymph Node-Negative) | ||
Hormone receptor-positive | Endocrine therapy ± chemotherapy | Consider genomic testing |
Hormone receptor-negative | Chemotherapy | |
HER-2-positive | Trastuzumab and chemotherapy | |
II (Lymph Node-Positive), III | ||
Hormone receptor-positive | Chemotherapy + endocrine therapy | Endocrine therapy should be recommended for all patients |
Hormone receptor-negative | Chemotherapy | Decision-making for chemotherapy may be influenced by results from ongoing clinical trials |
HER-2-positive | Trastuzumab and chemotherapy | Consider neoadjuvant chemotherapy with dual HER-2-targeted therapy |
HER-2, Human epidermal growth factor receptor 2.
From Townsend CM et al: Sabiston textbook of surgery, ed 21, St Louis, 2022, Elsevier.
TABLE 13 Breast Cancer Intrinsic Subtypes
Subtype | Characteristics | Markers |
---|---|---|
Luminal A | Low grade. High ER ∼40% of all breast cancer Good prognosis | ER+, PR+, HER2-Low Ki-67 (<14%) |
Luminal B | Higher grade. Lower ER ∼20% of all breast cancer Poorer prognosis than luminal A | ER+, PR+/-, HER2+/-High Ki-67 (>14%) |
HER2-enriched | High grade. Often node positive P53 mutations ∼10%-15% of all breast cancer | ER-, PR-, HER2+ |
Basal-like | High proliferation. BRCA dysfunction ∼15%-20% of all breast cancer Poor prognosis | ER-, PR-, HER2-CK5/6 Or EGFR+ |
CK, Cytokeratin; EGFR, epidermal growth factor receptor; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor.
From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.
TABLE 14 Treatment According to Breast Cancer Subtype
Subtype | Treatment Response and Prognosis | ||
---|---|---|---|
Luminal A | Respond to endocrine therapy | ||
Luminal B | Response to endocrine therapy lower. Response to chemotherapy greater than luminal A | ||
HER2-enriched | Respond to anti-HER2 agents (trastuzumab, pertuzumab, lapatinib) | ||
Basal-like | No response to endocrine therapy or anti-HER2 agents. Chemotherapy only treatment outside of a clinical trial |
AIs, Aromatase inhibitors; HER2, human epidermal growth factor receptor 2; SERMs, selective estrogen receptor modulators.
From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.
TABLE 10 Carcinoma In Situ: Lobular Versus Ductal
Feature | Lobular Carcinoma In Situ | Ductal Carcinoma In Situ |
---|---|---|
Age | Younger | Older |
Palpable mass | No | Uncommon |
Mammographic appearance | Not detected on mammography | Microcalcifications, mass |
Immunophenotype | E-cadherin negative | E-cadherin positive |
Usual manifestation | Incidental finding on breast biopsy | Microcalcifications on mammography or breast mass |
Bilateral involvement | Common | Uncertain |
Risk and site of subsequent breast cancer | 25% risk for invasive breast cancer in either breast over remaining lifespan | At site of initial lesion; 0.5% risk/yr of invasive breast cancer in opposite breast |
Prevention | Consider tamoxifen or raloxifene | Consider tamoxifen or raloxifene if estrogen-receptor positive |
Treatment | Yearly mammography and breast examination | Lumpectomy ± radiation; mastectomy for large or multifocal lesions |
From Goldman L, Schafer AI: Goldmans Cecil medicine, ed 24, Philadelphia, 2012, Saunders.
TABLE 11 Adjuvant Treatment Guidelines for Patients With Early-Stage Invasive Breast Cancer
Patient Group | Treatment | ||
---|---|---|---|
Hormone Receptor-Positive and HER2 Positive Breast Cancer | |||
<0.5 cm | Consider adjuvant endocrine therapy | ||
0.6-1 cm | Adjuvant endocrine therapy Consider adjuvant chemotherapy and trastuzumab | ||
>1 cm | Adjuvant endocrine therapy Adjuvant chemotherapy and trastuzumab | ||
Node positive | Adjuvant endocrine therapy Adjuvant chemotherapy with pertuzumab and trastuzumab | ||
Hormone Receptor-Positive and HER2 Negative Breast Cancer | |||
<0.5 cm | No adjuvant therapy | ||
>0.5 cm | Adjuvant hormonal therapy Consider adjuvant chemotherapy based on 21-gene recurrence score | ||
Node-positive | Adjuvant hormonal therapy + adjuvant chemotherapy | ||
Hormone Receptor-Negative and HER2 Positive Breast Cancer | |||
<0.5 cm | Consider adjuvant chemotherapy and trastuzumab | ||
0.6-1 cm | Consider adjuvant chemotherapy and trastuzumab | ||
>1 cm | Adjuvant chemotherapy and trastuzumab | ||
Node positive | Adjuvant endocrine therapy Adjuvant chemotherapy with pertuzumab and trastuzumab | ||
Hormone Receptor-Negative and HER2 Negative Breast Cancer | |||
≤0.5 cm | No adjuvant therapy | ||
0.6-1.0 cm | Consider adjuvant chemotherapy | ||
>1 cm or node positive | Adjuvant chemotherapy |
HER2, Human epidermal growth factor receptor 2.
Modified from National Comprehensive Cancer Network Guidelines. Available at www.nccn.org.
BOX 5 Options for Breast Reconstruction
Autogenous
Latissimus dorsi musculocutaneous flap Gluteal flap∗ Rubens flap∗ Lateral thigh flap∗ |
From Townsend CM et al: Sabiston textbook of surgery, ed 21, St Louis, 2022, Elsevier.
Figure E4 Breast-conserving surgery.
A, Incisions to remove malignant tumors are placed directly over the tumor or around the areola. After the partial mastectomy has been completed, the parenchymal defect is closed (inset) to prevent a cosmetic deformity. B, A transverse incision below the axillary hairline is used for sentinel node biopsy or axillary dissection. The boundaries of the axillary dissection are the axillary vein superiorly, the latissimus dorsi muscle laterally, and the chest wall medially. The inferior dissection enters the tail of Spence (the axillary tail of the breast). In sentinel node biopsy, a similar transverse incision is made, which may be located by percutaneous mapping with the gamma probe to detect a hot spot from the radiolabeled colloid. It is extended through the clavipectoral fascia, and the true axilla is entered. The sentinel node is located by staining with blue dye (inset), radioactivity, or both and is dissected free as a single specimen.
From Townsend CM et al: Sabiston textbook of surgery, ed 21, St Louis, 2022, Elsevier.
Follow-up after treatment of early breast cancer stages includes:
B, Female Breast Cancer Incidence by Race and Ethnicity (SEER Data). C, When Lobular Breast Cancer Metastasizes, It Can Often Infiltrate Serosal Surfaces, Mimicking Ovarian Cancer. This Patient Presented with Abdominal Bloating, Tightness, and Narrowing in Her Stool Caliber 9 Yr after the Diagnosis of a Stage I Breast Cancer. Note the Diffuse Thickening of the Rectal and Colonic Wall, Peritoneal Carcinomatosis, and Ascites. Fig. E6 (Continued)A Colonoscopy was Performed, and Biopsy Confirmed Diffuse Involvement with Metastatic Adenocarcinoma Consistent with a Breast Primary. On Restaging, She was Also Noted to have Multiple Osseous Metastases. D, In an Ultrasound-Guided Needle Biopsy, the Ultrasound Probe is Used to Localize the Lesion that was Identified Either on Physical Examination or on Mammogram. A Biopsy Needle is Passed through the Lesion Several Times to Obtain Tissue. Compared to a Stereotactic Biopsy, an Ultrasound-Guided Biopsy is Faster and Better Tolerated by Most Patients. However, Not All Lesions May Be Amenable to an Ultrasound-Guided Biopsy. E, The Premise Behind Stereotactic Needle Biopsy is that a Lesion Can Be Localized in 3D by Evaluating its Changes in Position in a Series of Angled Radiographic Views. First, a Radiograph Localizes the Suspicious Area; Then Two Additional Views, Angled 15 Degrees to Either Side of the Lesion, are Obtained. A Computer Calculates How Much the Lesions Position Appears to have Changed on Each of the Angled Views and Uses These Data to Estimate the Lesions Location Within 3D Space. With the Advent of Digital Mammography, These Images are Commonly Acquired Digitally. F, Positron Emission Tomography (PET) Involves Injection of a Substance Labeled with a Positron-Emitting Isotope (Commonly, Fluorine-18 Bound to D-Glucose, Called FDG for 2-([18F]fluoro-2-Deoxy-D-Glucose)). Metabolically Active Cells, Especially Malignant Ones, Preferentially Take Up Glucose and Therefore FDG, as Compared with Nonneoplastic Tissue. Sensitivity of PET Can Vary Considerably by Tumor Type and Size. False-Positive Results Can Occur in Areas of Inflammation or Infection. Many Machines Now Acquire CT Images in Tandem with PET Images, Which Can Then Be Fused Together to Provide Anatomic Correlation by CT with Metabolic Activity Measurements by PET. This Patient Presented with Palpable Axillary Adenopathy and a Large Breast Mass with Associated Erythema, Skin Edema, and Nipple Retraction. Note the Extremely Intense Areas of Uptake Within the Right Breast and Axilla Corresponding to the Patients Known Locally Advanced Breast Cancer. Also Note the Intense Uptake in the Right Supraclavicular, Paratracheal, Prevascular, Precarinal, and Hilar Lymph Nodes Suspicious for Metastatic Disease. Uptake in the Kidney, Bladder, and Ureters is Physiologic and Due to FDG Excretion. Uptake in the Right Adnexa and Jaw is Most Likely Physiologic and Benign. G, Panels 1 and 2: Accelerated Partial Breast Irradiation (APBI) Encompasses Techniques Including Intracavitary and Interstitial Brachytherapy as Well as 3D-Conformal, Intensity-Modulated, and Intraoperative External-Beam Radiation Therapy. One of the More Commonly Used Brachytherapy Methods in the U.S., the Mammosite Brachytherapy System (Hologic, Massachusetts), Involves Insertion of a Catheter with a Balloon Tip into the Lumpectomy Cavity at the Time of Surgery or Shortly Thereafter (Panel 1). The Balloon is Filled with Saline, and a High-Dose-Rate Radioactive Source is Introduced Twice Per Day for 5 Days by Computed Axial Tomography Scan-Based Treatment Planning, Permitting a Highly Conformal Dose to Be Delivered to the First Centimeter of Remaining Breast Tissue with Optimal Sparing of the Remaining Tissue and Other Regional Organs (Panel 2). The Balloon Catheter is Removed Upon Completion. APBI is an Option Only for Selected Patients, Mainly Older Women with Smaller, Node-Negative low-Risk Tumors and with Negative Margins. H, The HER Family of Receptors (Human Epidermal Growth Factor Receptor, Also Called ErbB, is a Group of Transmembrane Tyrosine Kinase Receptors that Regulate Cell Growth, Survival, and Differentiation Via a Variety of Pathways, Including RAS (Rat Sarcoma), RAF (Receptor Activation Factor), MAPK (Mitogen-Activated Protein Kinase), and MEK (Mitogen Extracellular Signal Kinase). The Tyrosine Kinase Domains are Activated by Dimerization. Current Therapeutics Involve Tyrosine Kinase Inhibitors (E.g., Lapatinib) and Antibodies Directed Against the HER2 Protein and VEGF (Vascular Endothelial Growth Factor) (E.g., Trastuzumab and Bevacizumab). Akt, Protein Kinase B; Pi3-K, Phosphatidylinositol 3-Kinase; SOS, Son of Sevenless.
From Skarin AT: Atlas of diagnostic oncology, ed 4, Philadelphia, 2010, Elsevier. Image courtesy of Drs. Pamela Dipiro and Wendy Chen, Dana Farber Cancer Institute, Boston, MA. Image courtesy of Robyn L. Birdwell, MD, Brigham and Womens Hospital, Boston, MA, and Diagnostic Imaging Breast, Amirsys, Inc., Salt Lake City, UT, 2006. Courtesy of Phillip M. Devlin, MD, Dana Farber/Brigham and Womens Cancer Center, Harvard Medical School, Boston, MA.
TABLE 17 Breast Cancer Screening Recommendations by Organization
Organization | When to Initiate Screening | Frequency of Screening | When to Stop Screening |
---|---|---|---|
American Academy of Family Physicians (AAFP) | Follow U.S. Preventive Services Task Force (USPSTF) recommendations | Follow USPSTF recommendations | Follow USPSTF recommendations |
American Cancer Society (ACS) | Opportunity to begin screening at ages 40-44 Regular screening starting at age 45 | Annually from age 45-54 Biennially starting at age 55 with opportunity to continue annually | Continue screening mammography as long as overall health is good, and life expectancy is 10 yr or longer |
American College of Obstetricians and Gynecologists (ACOG) | Annual screening starting at age 40 | Annually | Not specified |
American College of Physicians (ACP) | Individualized for women ages 40-49 Regular screening starting at age 50 | Biennially | Age 75 yr or older Women of any age with life expectancy <10 yr |
American College of Radiology (ACR) | Annual screening starting at age 40 | Annually | Should be considered as long as the patient is in good health and is willing to undergo additional testing if an abnormality is detected |
National Comprehensive Cancer Network (NCCN) | Annual screening starting at age 40 | Annually | Upper age limit is not yet established Consider comorbid conditions limiting life expectancy (e.g., ≤10 yr) and whether therapeutic interventions are planned |
U.S. Preventive Services Task Force (USPSTF) | Individualized for women ages 40-49 Regular screening beginning at age 50 | Biennially | Insufficient evidence to recommend for or against screening at age 75 or older |
From Niederhuber JE: Abeloffs clinical oncology, ed 6, Philadelphia, 2020, Elsevier.
BOX 7 Counseling Points for Women With Average Risk Interested in Contralateral Prophylactic Mastectomy (CPM)
From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.
Breast Cancer (Patient Information)
Breast Cancer: For Men (Patient Information)
Breast Abscess (Related Key Topic)
Fibrocystic Breast Disease (Related Key Topic)