Sections

Presentation

History

Many early breast carcinomas are asymptomatic, particularly if they were discovered during a breast-screening program. Larger tumors may present as a painless mass. Pain or discomfort is not usually a symptom of breast cancer; only 5% of patients with a malignant mass present with breast pain.

Often, the purpose of the history is not diagnosis but risk assessment. A family history of breast cancer in a first-degree relative is the most widely recognized breast cancer risk factor.

The US Preventive Services Task Force (USPSTF) has updated its 2005 guidelines on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. The current USPSTF recommendations are as follows^[80]:

Women who have family members with breast, ovarian, tubal, or peritoneal cancer should be screened to identify a family history that may be associated with an increased risk for mutations in the breast cancer susceptibility genes BRCA1 or BRCA2
Women who have positive screening results should receive genetic counseling and then BRCA testing if warranted
Women without a family history associated with an increased risk for mutations should not receive routine genetic counseling or BRCA testing

Physical Examination

If the patient has not noticed a lump, then signs and symptoms indicating the possible presence of breast cancer may include the following:

Change in breast size or shape
Skin dimpling or skin changes (eg, thickening, swelling, or redness)
Recent nipple inversion or skin change or other nipple abnormalities (eg, ulceration, retraction, or spontaneous bloody discharge)
Nipple discharge, particularly if bloodstained
Axillary lump

To detect subtle changes in breast contour and skin tethering, the examination must include an assessment of the breasts with the patient upright with arms raised. The following findings should raise concern:

Lump or contour change
Skin tethering
Nipple inversion
Dilated veins
Ulceration
Mammary Paget disease
Edema or peau d’orange

The nature of palpable lumps is often difficult to determine clinically, but the following features should raise concern:

Hardness
Irregularity
Focal nodularity
Asymmetry with the other breast
Fixation to skin or muscle (assess fixation to muscle by moving the lump in the line of the pectoral muscle fibers with the patient bracing her arms against her hips)

A complete examination includes assessment for lymphatic and distant metastases; in descending order of frequency, distant metastases are to bone, lung, liver, and brain.^[81]Thus, the assessment should include the axillae and supraclavicular fossae, the chest and sites of skeletal pain, and abdominal and neurologic examinations. The clinician should be alert to symptoms of metastatic spread, such as the following:

Bone pain
Symptoms of hypercalcemia
Breathing difficulties
Abdominal distention
Jaundice
Localizing neurologic signs
Altered cognitive function
Headache

The clinical evaluation should include a thorough assessment of specific risk factors for breast cancer (see Breast Cancer Risk Factors).

Differential Diagnoses

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Media Gallery

Anatomy of the breast.
Intrinsic subtypes of breast cancer.
Breast cancer. Intraductal carcinoma, comedo type. Distended duct with intact basement membrane and central tumor necrosis.
Breast cancer. Intraductal carcinoma, noncomedo type. Distended duct with intact basement membrane, micropapillary, and early cribriform growth pattern.
Breast cancer. Lobular carcinoma in situ. Enlargement and expansion of lobule with monotonous population of neoplastic cells.
Breast cancer. Lobular carcinoma in situ. Enlargement and expansion of lobule with monotonous population of neoplastic cells.
Breast cancer. Infiltrating ductal carcinoma. Low-grade carcinoma with well-developed glands invading fibrous stroma.
Breast cancer. Colloid (mucinous) carcinoma. Nests of tumor cells in pool of extracellular mucin.
Breast cancer. Papillary carcinoma. Solid papillary growth pattern with early cribriform and well-developed thin papillary fronds.
Anatomy of the breast. Courtesy of Wikimedia Commons (Patrick J Lynch, medical illustrator).

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Author

Pavani Chalasani, MD, MPH Associate Professor of Medicine (Tenure), Section of Hematology/Oncology, Department of Medicine, Arizona Health Sciences Center, University of Arizona College of Medicine

Pavani Chalasani, MD, MPH is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Hemostasis and Thrombosis Research Society, SWOG

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bayer, Heron, Amgen, Athenex, Novartis, Eisai, Eli Lilly, Zentalis <br/>Received research grant from: Pfizer.

Chief Editor

John V Kiluk, MD, FACS Associate Professor, Department of Oncologic Sciences, Department of Surgery (Joint Appointment), University of South Florida Morsani College of Medicine; Clinical Director, Breast Surgical Oncology, Associate Member, Comprehensive Breast Program, Department of Women's Oncology, H Lee Moffitt Cancer Center and Research Institute

John V Kiluk, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society of Breast Surgeons, Moretz Surgical Society, Society of Surgical Oncology, Southeastern Surgical Congress

Disclosure: Nothing to disclose.

Additional Contributors

Alison T Stopeck, MD Professor of Medicine, Arizona Cancer Center, University of Arizona Health Sciences Center; Director of Clinical Breast Cancer Program, Arizona Cancer Center; Medical Director of Coagulation Laboratory, University Medical Center; Director of Arizona Hemophilia and Thrombosis Center

Alison T Stopeck, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, SWOG, American Society of Clinical Oncology, Hemophilia and Thrombosis Research Society

Disclosure: Received honoraria from Genentech for speaking and teaching; Received honoraria from AstraZeneca for speaking and teaching; Received grant/research funds from AstraZeneca for other.

Patricia A Thompson, PhD Assistant Professor, Department of Pathology, University of Arizona College of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Leona Downey, MD Assistant Professor of Internal Medicine, Section of Oncology and Hematology, University of Arizona, Arizona Cancer Center

Leona Downey, MD is a member of the following medical societies: American Geriatrics Society, American Society of Clinical Oncology, and Southwest Oncology Group

Disclosure: Nothing to disclose.

Manjit Singh Gohel, MD, MRCS, MB, ChB Specialist Registrar, Division of Breast and Endocrine Surgery, Northwick Park Hospital

Disclosure: Nothing to disclose.

Harold Harvey, MD Professor, Department of Medicine, Pennsylvania State University

Disclosure: Nothing to disclose.

Kanchan Kaur, MBBS, MS (General Surgery), MRCS (Ed) Consulting Breast and Oncoplastic Surgeon, Medanta, The Medicity, India

Disclosure: Nothing to disclose.

Julie Lang, MD Assistant Professor of Surgery and the BIO5 Institute, Director of Breast Surgical Oncology, University of Arizona College of Medicine

Julie Lang, MD is a member of the following medical societies: American College of Surgeons, American Society of Breast Surgeons, American Society of Clinical Oncology, Association for Academic Surgery, and Society of Surgical Oncology

Disclosure: Genomic Health Grant/research funds Speaking and teaching; Agendia Grant/research funds Speaking and teaching; Surgical Tools Grant/research funds Research; Sysmex Grant/research funds Research

Robert B Livingston, MD Professor of Clinical Medicine and Director, Clinical Research Shared Services, Arizona Cancer Center

Robert B Livingston, MD is a member of the following medical societies: American Association for Cancer Research, American Federation for Clinical Research, and American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Hanan Makhoul, MD Staff Physician, Department of Internal Medicine, University of Arkansas School of Medicine

Disclosure: Nothing to disclose.

Issam Makhoul, MD Associate Professor, Department of Medicine, Division of Hematology/Oncology, University of Arkansas for Medical Sciences

Issam Makhoul, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology

Disclosure: Nothing to disclose.

Robert C Shepard, MD, FACP Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International

Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy

Disclosure: Nothing to disclose.

Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) Senior Lecturer, Director of Breast Service, Department of Surgery, Imperial College School of Medicine; Consultant Surgeon, Northwick Park and St Marks Hospitals, UK

Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada and Royal College of Surgeons of Edinburgh

Disclosure: Nothing to disclose.

Carl V Smith, MD The Distinguished Chris J and Marie A Olson Chair of Obstetrics and Gynecology, Professor, Department of Obstetrics and Gynecology, Senior Associate Dean for Clinical Affairs, University of Nebraska Medical Center

Carl V Smith, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Council of University Chairs of Obstetrics and Gynecology, Nebraska Medical Association, and Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Wiley Souba, MD Chairman, Professor, Department of General Surgery, Pennsylvania State College of Medicine; Chief Surgeon, The Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Rachel Swart, MD, PhD Assistant Professor of Medicine, Department of Hematology and Oncology, Arizona Cancer Center, University of Arizona

Rachel Swart, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, Arizona Medical Association, and Southwest Oncology Group

Disclosure: Roche Grant/research funds Other

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Simon Thomson, MB, BCh, MD, FRCS Specialist Registrar, Department of Breast and Endocrine Surgery, Northwick Park Hospital, UK

Simon Thomson, MB, BCh, MD, FRCS is a member of the following medical societies: British Medical Association

Disclosure: Nothing to disclose.

Modality	Sensitivity	Specificity	PPV	Indications
Mammography	63-95% (>95% palpable, 50% impalpable, 83-92% in women older than 50 y; decreases to 35% in dense breasts)	14-90% (90% palpable)	10-50% (94% palpable)	Initial investigation for symptomatic breast in women older than 35 y and for screening; investigation of choice for microcalcification
Ultrasonography	68-97% palpable	74-94% palpable	92% (palpable)	Initial investigation for palpable lesions in women younger than 35 y
MRI	86-100%	21-97% (< 40% primary cancer)	52%	Scarred breast, implants, multifocal lesions, and borderline lesions for breast conservation; may be useful in screening high-risk women
Scintigraphy	76-95% palpable, 52-91% impalpable	62-94% (94% impalpable)	70-83% (83% palpable, 79% impalpable)	Lesions >1 cm and axilla assessment; may help predict drug resistance
PET	96% (90% axillary metastases)	100%		Axilla assessment, scarred breast, and multifocal lesions
MRI = magnetic resonance imaging; PET = positron emission tomography; PPV = positive predictive value.

	Score
	1	> 2	> 3
A. Tubule formation	>75%	10-75%	< 10%
B. Mitotic count/HPF (microscope- and field-dependent)	< 7	7-12	>12
C. Nuclear size and pleomorphism	Near normal; little variation	Slightly enlarged; moderate variation	Markedly enlarged; marked variation
Grade I cancer if total score (A + B + C) is 3-5
Grade II cancer if total score (A + B + C) is 6 or 7
Grade III cancer if total score (A + B + C) is 8 or 9
HPF = high-power field.

DCIS Characteristic	Comedo	Noncomedo
Nuclear grade	High	Low
Estrogen receptor	Often negative	Positive
Distribution	Continuous	Multifocal
Necrosis	Present	Absent
Local recurrence	High	Low
Prognosis	Worse	Better
DCIS = ductal carcinoma in situ.

Primary tumor (T)
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Tis	Carcinoma in situ
Tis (DCIS)	Ductal carcinoma in situ
Tis (Paget)	Paget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized on the basis of 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 (round any measurement >1.0-1.9 mm to 2 mm)
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), not including invasion of dermis alone
T4a	Extension to chest wall, not including only pectoralis muscle adherence/invasion
T4b	Ulceration and/or ipsilateral satellite nodules and/or edema (including peau d’orange) of the skin, which do not meet the criteria for inflammatory carcinoma
T4c	Both T4a and T4b
T4d	Inflammatory carcinoma
Regional lymph nodes (N)
Clinical
cNX	Regional lymph nodes cannot be assessed (eg, previously removed)
cN0	No regional lymph node metastasis (on imaging or clinical examination)
cN1	Metastasis to movable ipsilateral level I, II axillary lymph node(s)
cN1mi	Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm)
cN2	Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted; or in ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases
cN2a	Metastases in ipsilateral level I, II axillary lymph nodes fixed to one another (matted) or to other structures
cN2b	Metastases only in ipsilateral internal mammary nodes and in the absence of axillary lymph node metastases
cN3	Metastases in ipsilateral infraclavicular (level III axillary) lymph node(s), with or without level I, II axillary node involvement, or in ipsilateral internal mammary lymph node(s) with level I, II axillary lymph node metastasis; or metastases in ipsilateral supraclavicular lymph node(s), with or without axillary or internal mammary lymph node involvement
cN3a	Metastasis in ipsilateral infraclavicular lymph node(s)
cN3b	Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s)
cN3c	Metastasis in ipsilateral supraclavicular lymph node(s)
Note: (sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or fine needle aspiration/core needle biopsy, respectively.
Pathologic (pN)
pNX	Regional lymph nodes cannot be assessed (for example, previously removed, or not removed for pathologic study)
pN0	No regional lymph node metastasis identified histologically, or isolated tumor cell clusters (ITCs) only. Note: ITCs are defined as small clusters of cells ≤ 0.2 mm, or single tumor cells, or a cluster of < 200 cells in a single histologic cross-section; ITCs may be detected by routine histology or by immunohistochemical (IHC) methods; nodes containing only ITCs are excluded from the total positive node count for purposes of N classification but should be included in the total number of nodes evaluated
pN0(i)	No regional lymph node metastases histologically, negative IHC
pN0(i+)	ITCs only in regional lymph node(s)
pN0(mol-)	No regional lymph node metastases histologically, negative molecular findings (reverse transcriptase polymerase chain reaction [RT-PCR])
pN0(mol+)	Positive molecular findings by RT-PCR; no ITCs detected
pN1	Micrometastases; or metastases in 1-3 axillary lymph nodes and/or in internal mammary nodes; and/or in clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy
pN1mi	Micrometastases (200 cells, > 0.2 mm but none > 2.0 mm)
pN1a	Metastases in 1-3 axillary lymph nodes (at least 1 metastasis > 2.0 mm)
pN1b	Metastases in ipsilateral internal mammary lymph nodes, excluding ITCs, detected by sentinel lymph node biopsy
pN1c	Metastases in 1-3 axillary lymph nodes and in internal mammary sentinel nodes (ie, pN1a and pN1b combined)
pN2	Metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases
pN2a	Metastases in 4-9 axillary lymph nodes (at least 1 tumor deposit > 2.0 mm)
pN2b	Clinically detected* metastases in internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary lymph nodes
pN3	Metastases in ≥ 10 axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in > 3 axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes
pN3a	Metastases in ≥ 10 axillary lymph nodes (at least 1 tumor deposit > 2.0 mm); or metastases to the infraclavicular (level III axillary lymph) nodes
pN3b	pN1a or pN2a in the presence of cN2b (positive internal mammary nodes by imaging) or pN2a in the presence of pN1b
pN3c	Metastases in ipsilateral supraclavicular lymph nodes
*"Clinically detected" is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy or a presumed pathologic macrometastasis on the basis of FNA biopsy with cytologic examination.
Distant metastasis (M)
M0	No clinical or radiographic evidence of distant metastasis
cM0(i+)	No clinical or radiographic evidence of distant metastases in the presence of tumor cells or deposits no larger than 0.2 mm detected microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastase
cM1	Distant metastases detected by clinical and radiographic means
pM1	Any histologically proven metastases in distant organs; or if in non-regional nodes, metastases > 0.2 mm

Histologic grade (G)
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	T	N	M
0	Tis	N0	M0
IA	T1	N0	M0
IB	T0	N1mi	M0
	T1	N1mi	M0
IIA	T0	N1	M0
	T1	N1	M0
	T2	N0	M0
IIB	T2	N1	M0
	T3	N0	M0
IIIA	T0	N2	M0
	T1	N2	M0
	T2	N2	M0
	T3	N1	M0
	T3	N2	M0
IIIB	T4	N0	M0
	T4	N1	M0
	T4	N2	M0
IIIC	Any T	N3	M0
IV	Any T	Any N	M1

TNM	Grade	HER2	ER	PR	Stage
Tis N0 M0	Any	Any	Any	Any	0
T1 N0 M0 T0 N1mi M0 T1 N1mi M0	G1	Positive	Positive	Positive	IA
				Negative
			Negative	Positive
				Negative
		Negative	Positive	Positive
				Negative
			Negative	Positive
				Negative	IB
	G2	Positive	Positive	Positive	IA
				Negative
			Negative	Positive
				Negative
		Negative	Positive	Positive
				Negative
			Negative	Positive
				Negative	IB
	G3	Positive	Positive	Positive	IA
				Negative
			Negative	Positive
				Negative
		Negative	Positive	Positive
				Negative	IB
			Negative	Positive
				Negative
T0 N1 M0 T1 N1 M0 T2 N0 M0	G1	Positive	Positive	Positive	IB
				Negative	IIA
			Negative	Positive
				Negative
		Negative	Positive	Positive	IB
				Negative	IIA
			Negative	Positive
				Negative
	G2	Positive	Positive	Positive	IB
				Negative	IIA
			Negative	Positive
				Negative
		Negative	Positive	Positive	IB
				Negative	IIA
			Negative	Positive
				Negative	IIB
	G3	Positive	Positive	Positive	IB IIA
				Negative
			Negative	Positive
				Negative
		Negative	Positive	Positive
				Negative	IIB
			Negative	Positive
				Negative
T2 N1 M0 T3 N0 M0	G1	Positive	Positive	Positive	IB
				Negative	IIA
			Negative	Positive
				Negative	IIB
		Negative	Positive	Positive	IIA
				Negative	IIB
			Negative	Positive
				Negative
	G2	Positive	Positive	Positive	IB
				Negative	IIA
			Negative	Positive
				Negative	IIB
		Negative	Positive	Positive	IIA
				Negative	IIB
			Negative	Positive
				Negative	IIIB
	G3	Positive	Positive	Positive	IB
				Negative	IIB
			Negative	Positive
				Negative
		Negative	Positive	Positive
				Negative	IIIA
			Negative	Positive
				Negative	IIIB
T0 N2 M0 T1 N2 M0 T2 N2 M0 T3 N1 M0 T3 N2 M0	G1	Positive	Positive	Positive	IIA
				Negative	IIIA
			Negative	Positive
				Negative
		Negative	Positive	Positive	IIA
				Negative	IIIA
			Negative	Positive
				Negative	IIIB
	G2	Positive	Positive	Positive	IIA
				Negative	IIIA
			Negative	Positive
				Negative
		Negative	Positive	Positive	IIA
				Negative	IIIA
			Negative	Positive
				Negative	IIIB
	G3	Positive	Positive	Positive	IIB
				Negative	IIIA
			Negative	Positive
				Negative
		Negative	Positive	Positive
				Negative	IIIB
			Negative	Positive
				Negative	IIIC
T4 N0 M0 T4 N1 M0 T4 N2 M0 Any T N3 M0	G1	Positive	Positive	Positive	IIIA
				Negative	IIIB
			Negative	Positive
				Negative
		Negative	Positive	Positive
				Negative
			Negative	Positive
				Negative	IIIC
	G2	Positive	Positive	Positive	IIIA
				Negative	IIIB
			Negative	Positive
				Negative
		Negative	Positive	Positive
				Negative
			Negative	Positive
				Negative	IIIC
	G3	Positive	Positive	Positive	IIIB
				Negative
			Negative	Positive
				Negative
		Negative	Positive	Positive
				Negative	IIIC
			Negative	Positive
				Negative
Any T Any N M1	Any	Any	Any	Any	IV
ER=estrogen receptor; PR=progesterone receptor

Agent	Dose and Schedule
Postmenopausal
Tamoxifen	20 mg PO every day
Elacestrant	345 mg PO every day
Or
Aromatase inhibitor
Anastrozole	1 mg PO every day
Letrozole	2.5 mg PO every day
Exemestane	25 mg PO every day
Or
Fulvestrant	500 mg IM on days 1, 15, 29, and once monthly thereafter
Or
Megestrol	40 mg PO 4 times a day
Premenopausal
Tamoxifen	20 mg PO every day
Or
Aromatase inhibitor + LHRH*
Leuprolide	7.5 mg IM depot q28d 22.5 mg IM q3mo 30 mg IM q4mo
Goserelin	3.6 mg SC depot q28d 10.8 mg SC q3mo
Megestrol	40 mg PO 4 times a day
*LHRH = luteinizing hormone–releasing hormone.

Drug	Class	Dose/Schedule	Overall Response Rate (ORR)	Toxicity
Abemaciclib	CDK inhibitor	200 mg PO BID continue until disease progression	19.7%	Diarrhea, fatigue, neutropenia and nausea
Capecitabine	Oral fluoro-pyrimidine	1250 mg/m²/d PO for 2 weeks with 1 wk off	30%	Rash, hand-foot syndrome, diarrhea, mucositis
Docetaxel	Antimicrotubule	75-100 mg/m² IV q3wk or 40 mg/m²/wk X IV for 6 wk with 2 wk off	30-68%	Myelosuppression, alopecia, skin reaction, mucositis, and fluid retention
Doxorubicin	Anthracycline (antitumor antibiotic)	45-60 mg/m² IV q3wk or 20 mg/m² IV qwk (not to exceed a cumulative dose of 450-500 mg/m²)	35-50%	Myelosuppression, nausea/ vomiting, mucositis, diarrhea cardiotoxicity, alopecia
Doxil (liposomal encapsulated doxorubicin)	Anthracycline	20 mg/m² IV q2wk or 35-40 mg/m² IV q4wk		Less cardiotoxicity, neutropenia, alopecia, stomatitis, hand-foot syndrome
Epirubicin	Anthracycline	90 mg/m² IV q3wk (not to exceed cumulative dose of 900 mg/m²)	35-50%	Myelosuppression, mucositis, nausea, vomiting, cardiotoxicity
Gemcitabine	Antimetabolite	725 mg/m²/wk IV for 3 wk then 1 wk off or 1 g/m²/wk IV X 2 then 1 wk off		Myelosuppression, nausea/ vomiting, flulike syndrome, elevated LFTs
Nab-paclitaxel	Antimicrotubule	80-100 mg/m²/wk IV X 3 then 1 wk off or 260 mg/m² IV q3wk	58-62% 33%	Less neuropathy, and allergic reaction
Olaparib	PARP inhibitor	300 mg PO BID	59.9%	Anemia, fatigue, nausea, and vomiting
Paclitaxel	Antimicrotubule	80 mg/m²/wk IV or 175 mg/m² IV over 3 hours q3wk	25-50%	Myelosuppression, alopecia, neuropathy, allergic reaction
Pertuzumab	Monoclonal antibody	840 mg IV loading dose, then 420 mg q3wk Give with trastuzumab and docetaxel	80.2% (objective response rate)	Fever, allergic reaction, cardiotoxicity/congestive heart failure
Palbociclib	CDK inhibitor	125 mg/day PO for 3 weeks with 1 wk off Give with letrozole	Data are not available for ORR Mean PFS was 10.2 months in the letrozole group and 20.2 months for palbociclib plus letrozole group	Neutropenia, leukopenia, thrombocytopenia, anemia, stomatitis
Ribociclib	CDK inhibitor	600 mg/day PO for 3 weeks with 1 wk off Give with letrozole	Mean PFS was 16 months in the letrozole group and 25.3 months for ribociclib	QT prolongation, hepatobiliary toxicity, neutropenia, alopecia, diarrhea, vomiting, constipation, fatigue, anorexia
Sacituzumab govitecan	Monoclonal antibody	10 mg/kg IV on Days 1 and 8 with 2 wk off	33.3%	Nausea, neutropenia, diarrhea, fatigue, anemia, vomiting
Talazoparib	PARP inhibitor	1 mg PO qDay	62.6%	Fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and decreased appetite
Trastuzumab or biosimilars of trastuzumab	Monoclonal antibody	Combination therapy: 4 mg/kg IV once, then 2 mg/kg weekly for 12-18 weeks, then 6 mg/kg q3weeks to total 52 weeks Single agent: 8 mg/kg IV once, then 6 mg/kg q3weeks to total 52 weeks	10-15%	Fever, allergic reaction, cardiotoxicity/congestive heart failure
Trastuzumab deruxtecan^[154]	Monoclonal antibody conjugate	5.4 mg/kg IV q3weeks	60.3%	Interstitial lung disease and pneumonitis; neutropenia; left ventricular dysfunction
Tucatinib^[155]	Tyrosine kinase inhibitor of HER2	300 mg PO BID	40.6%	Diarrhea, hand-foot syndrome, nausea, fatigue, hepatotoxicity
Vinorelbine	Vinca alkaloid	20 mg/m²/wk IV	35-45%	Myelosuppression, nausea/ vomiting, constipation, fatigue, stomatitis, anorexia

	NCCN	ASCO
History and physical examination	Year 1, every 3-4 mo Year 2, every 4 mo Year 3-5, every 6 mo Year 6+, annually	Year 1-3, every 3-6 mo Year 4-5, every 6-12 mo Year 6+, annually
Breast self-examination	No recommendation	Counseled to perform monthly breast self-examination
Mammography	6 mo after post-BCS radiation therapy Annually thereafter	6 mo after definitive radiation therapy Every 6-12 mo for surveillance of abnormalities Annually if stability of abnormalities is achieved
Pelvic examination	Annually, for women on tamoxifen Annual exam if uterus present	Regular gynecologic follow-up Patients on tamoxifen should be advised to report any vaginal bleeding
Routine blood tests	Not recommended	Not recommended
Imaging studies	Not recommended	Not recommended
Tumor marker testing	Not recommended	Not recommended

Breast Cancer Clinical Presentation

History

Physical Examination

References

Tables

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