General Breast Cancer

Updated by Katherine Osusky Castle

BACKGROUND

What are the 3 most commonly diagnosed cancers in women in decreasing order of incidence?

Most commonly diagnosed cancers in women: breast > lung > colorectal (Siegal R et al., Cancer Stats 2013)

What are the 3 most common causes of cancer death in women in decreasing order of incidence?

Most common causes of cancer death in women: lung > breast > colorectal (Siegal R et al., Cancer Stats 2013)

Approximately how many women are diagnosed with invasive and noninvasive breast cancer, and how many will die of breast cancer annually?

Incidence: ∼232,000 invasive breast cancers and ∼60,000 noninvasive breast cancers annually (Siegal R, Cancer Stats 2013)

Mortality: ∼40,000

What is median age of Dx for invasive breast cancer?

The median age for invasive breast cancer is 61 yrs. (Siegal R et al., Cancer Treatment and Survivorship Stats 2013)

What race has the highest rate of breast cancer Dx? What race has the highest rate of breast cancer mortality?

Highest Dx: whites

Highest mortality: blacks

(Siegal R, Cancer Stats 2013)

For women born in the U.S. in 2009, approximately what % will be diagnosed with breast cancer in their lifetimes?

~12% (1 in 8) of U.S. women born in 2009 will be diagnosed with breast cancer. (Siegal R et al., Cancer Stats 2013)

In the U.S. in 2009, was the incidence of breast cancer Dx increasing or decreasing?

The incidence of Dx was increasing. (Siegal R et al., Cancer Stats 2013)

In the U.S. in 2009, was the incidence of breast cancer mortality increasing or decreasing?

The incidence of mortality was decreasing. (Siegal R et al., Cancer Stats 2013)

What % of breast cancers are due to known hereditary mutations in single genes?

£10% (Foulkes WD et al., NEJM 2008)

What are the 2 most common hereditary mutations that predispose to breast cancer?

BRCA1 and BRCA2 are the most common mutations. (These are most common in the Ashkenazi Jewish population, where they are found in as many as 1 in 40.) (Metcalfe KA et al., JCO 2010)

Mutations in which gene, BRCA1 or BRCA2, confers a higher risk of ovarian cancer?

Both BRCA1 and BRCA2 are associated with increased risk of ovarian cancer, but risks are higher with BRCA1 (45% lifetime risk) compared to BRCA2 (15% lifetime risk). (Chen S et al., JCO 2007)

What are 2 other hereditary syndromes associated with an increased risk of breast cancer and their related germ line mutations?

Both are a result of mutations in tumor suppressor genes:

1. Li-Fraumeni syndrome: TP53

2. Cowden syndrome: PTEN

Is HRT with estrogen and progestin associated with an increased or decreased risk of breast cancer?

HRT with estrogen and progestin is associated with an increased RR of 1.7.

Separate the following factors into those that increase or decrease the risk of breast cancer: younger age at menarche, younger age at menopause, nulliparity, prolonged breastfeeding, use of HRT.

Increase risk: younger age at menarche, nulliparity, use of HRT

Decrease risk: younger age at menopause, prolonged breastfeeding

Estimate the annual risk of a contralat breast cancer in the 10 yrs following a primary Dx.

Premenopausal: 1%/yr

Postmenopausal: 0.5%/yr

What is the definition of natural menopause and what is the median age at which is occurs?

Definition: permanent cessation of menstrual periods (12 mos of amenorrhea) without other obvious pathologic or physiologic cause.

Median age: 51 yrs

What are the U.S. Preventive Services Task Force (USPSTF) screening recommendations for normal-risk women age <50 yrs, age 50–74 yrs, and age >74 yrs?

For normal-risk women age ≤50 yrs: avoid routine mammographic screening (individualized use acceptable)

For normal-risk women age 50–74 yrs: biennial mammogram

For normal-risk women age >74 yrs: insufficient evidence to assess balance of benefits and harms

For all women: insufficient evidence for or against clinical breast exam (CBE) as a supplement to mammography.

For all women: recommend against breast self-exam (harms outweigh benefits) (USPSTF, Ann Intern Med 2009)

What are the ACS screening recommendations for normal-risk women age 20–39 yrs and women ≥40 yrs?

For normal-risk women age 20–39 yrs: CBE at least every 3 yrs and optional breast self-exam.

For normal risk women ≥40: annual CBE and mammogram as well as optional breast self-exam with decision to discontinue routine screening individualized (no strict age cutoff)

(The USPSTF recommends biennial screening mammography beginning at ≥50 yo and discontinuation at age 74.)

For a woman with prior thoracic RT during the 2^nd and 3rd decades of life, when should screening begin for breast cancer and how?

According to NCCN guidelines:

Age ≤25: annual CBE beginning 8–10 yrs after RT

Age >25: annual mammogram + CBE every 6–12 mos and annual breast MRI beginning 8–10 yrs after RT or age 40 (whichever comes 1st).

When should a woman be screened for breast cancer using MRI?

ACS guidelines (2011) recommend screening MRI as a supplement to yearly mammography beginning at age 30 for women who have a high lifetime risk (>20%–25% risk). This includes those with BRCA1/2 mutations or a 1^st-degree relative with BRCA1/2 but who have not had personal genetic testing, those with high lifetime risk according to risk assessment tools based primarily on family Hx, those who had radiation to the chest at 10–30 years of age, and those with Li-Fraumeni or Cowden syndrome or with a 1^st-degree relative with 1 of these syndromes. This does not include women with a personal Hx of breast cancer without other risk factors or women with dense breast tissue.

According to NCCN 2013,what are the potential clinical indications and applications of dedicated breast MRI testing?

1. Define extent of cancer, multifocal or multicentric Dz in the ipsi breast.*

2. Screen for contralat breast cancer in a newly diagnosed breast cancer pt.

*Available data do not demonstrate that MRI improves local recurrence, survival, or detection in dense breasts.

3. Evaluate before and after neoadj therapy to define extent of Dz, response to Tx, and potential for breast conservation.

4. Detect additional Dz in women with mammographically dense breasts.*

5. Detect primary Dz in pts with +axillary LNs or Paget Dz of the nipple when primary is not identified on mammogram, US, or physical exam.

Breast MRIs should be performed only where there is a dedicated breast coil, an experienced radiologist, and capacity for MRI-guided biopsy. Since false+ findings on MRI are common, surgical decisions should not be based solely on MRI; additional tissue sampling should be performed in areas of concern identified by MRI.

Name the 5 rare histologic types of breast cancer that have a more favorable overall prognosis than invasive ductal/lobular carcinoma.

Rare types of breast cancer with a more favorable prognosis:

1. Tubular

2. Mucinous

3. Medullary (not including atypical medullary)

4. Cribriform

5. Invasive papillary

Name the 1 rare histologic type of breast cancer that has a less favorable overall prognosis than invasive ductal/lobular carcinoma.

Micropapillary carcinoma has a less favorable overall prognosis.

What is the Oncotype DX, and which breast cancer pts are eligible for its use?

Oncotype DX is a 21-gene assay that quantifies the likelihood of distant recurrence in tamoxifen-treated ER+, node– breast cancer patients. (Paik S et al., NEJM 2004) Evaluation of Oncotype DX in pts from NSABP B20 suggests that the recurrence score also predicts the magnitude of chemo benefit. (Paik S et al., JCO 2006) NCCN currently recommends the use of Oncotype DX in early stage, ER+, node– pts.

What are the 5 subtypes of the tissue microarray classification system for breast cancer? Which 2 subtypes carry poor prognoses?

Subtypes of the tissue microarray classification system:

1. Luminal A (↑ ER expressing, ↓ proliferation)

2. Luminal B (↑ ER expressing, ↓ proliferation)

3. HER2 overexpressing

4. Normal-like

5. Basal type (ER/progesterone receptor (PR)/HER2N–)

Basal and luminal B carry relatively poor prognoses.

What are phyllodes tumors of the breast, and what is the most important factor that determines risk of recurrence?

Phyllodes tumors are rare tumors containing both stromal and epithelial elements. Although the subtypes range from benign to malignant, the most important prognostic factor for recurrence is a clear margin after resection.

WORKUP/STAGING

What view(s) comprise a screening mammogram?

1. Mediolateral oblique: allows localization of tumor in superior-inferior dimensions

2. Craniocaudal: allows localization of tumor in medial-lateral dimensions

What is the workup for a breast lesion detected on screening mammogram?

Breast lesion workup: H&P (family Hx of breast and ovarian cancer, prior abnl mammograms, Hx of atypical ductal or lobular hyperplasia), diagnostic bilat mammogram (additional views including spot compression and magnification), and Bx of lesion (if mass nonpalpable, a stereotactic Bx should be performed).

What is the rate of axillary nodal positivity by T stage for breast cancer pts undergoing axillary dissection? What if the primary tumor is palpable vs. nonpalpable on exam?

ALL (nonpalpable/palpable)

(Silverstein M et al., World J Surg 2001)

What are the 5 regional LN stations in breast cancer?

Regional LN stations in breast cancer:

Station I: nodes inf/lat to pectoralis minor muscle

Station II: nodes deep to pectoralis minor

Station III: nodes sup/med to pectoralis minor

Station IV: supraclavicular nodes

Station V: internal mammary (IM) nodes

Infraclavicular nodes typically refer to the level III axillary nodes by radiation oncology.

What is the T staging for invasive breast cancer according to the AJCC 7th edition (2011)?

Tis: in situ (ductal carcinoma in situ [CIS], lobular CIS, or isolated Paget)

T1mi: microinvasion ≤1 mm

T1a: >0.1–0.5 cm

T1b: >0.5–1 cm

T1c: >1–2 cm

T2: >2–5 cm

T3: >5 cm

T4a: extension to chest wall, not including pectoralis muscle

T4b: edema (including peau d’orange) or ulceration of skin of breast, or ipsilateral satellite nodules, not meeting T4d criteria

T4c: both T4a and T4b

T4d: inflammatory carcinoma (erythema and edema over at least one-third of the breast, present for less than 6 mos, in conjunction with biopsy proof of invasive carcinoma)

(Note: T classification is the same whether it is based on clinical judgment or pathologic assessment. In general, pathologic determination should take precedence for determination of T size.)

Does involvement of the dermis alone qualify as T4 disease?

No. Involvement of the skin by breast cancer qualifies as T4 only if there is edema, ulceration, or skin nodules.

What is the clinical N staging for invasive breast cancer according to the AJCC 7th edition (2011)?

N1: movable ipsi level I/II axillary LN

N2a: ipsi level I/II axillary LNs fixed/matted

N2b: clinically apparent IM node in absence of clinically evident axillary nodes

N3a: ipsi infraclavicular LNs

N3b: ipsi IM and axillary nodes

N3c: ipsi supraclavicular nodes

What is the pathologic N staging for invasive breast cancer according to the AJCC 7th edition (2011)?

pN0(i–): negative by immunohistochemistry (IHC)

pN0(i+): positive by IHC only, but no cluster >0.2 mm (also called isolated tumor cell clusters)

pN0(mol-): negative by reverse transcription-polymerase chain reaction (RT-PCR)

pN0(mol+): positive by RT-PCR only

pN1mi: all nodal mets >0.2 mm or > 200 cells but ≤2 mm

pN1a: 1–3 axillary LNs involved, at least 1 >2 mm

pN1b: IM node detected by sentinel LND, but not clinically apparent

pN1c: 1–3 axillary nodes and IM node detected by sentinel LND, but not clinically apparent

pN2a: 4–9 axillary LNs involved, at least 1 >2 mm

pN2b: clinically apparent IM nodes in the absence of axillary LN mets

pN3a: >10 axillary LN or mets to infraclavicular (axillary level III) LNs

pN3b: clinically apparent IM node in the presence of axillary nodes; or ≥3 axillary LNs and IM node detected by sentinel LND, but not clinically apparent

pN3c: ipsi supraclavicular node

Define the AJCC breast cancer stage groupings using TNM status.

Stage 0: Tis, N0

Stage IA: T1, N0

Stage IB: T1, N1mic

Stage IIA: T2, N0 or T0-T1, N1

Stage IIB: T3, N0 or T2, N1

Stage IIIA: T3, N1 or T0-T3, N2

Stage IIIB: T4, N0-N2

Stage IIIC: any T, N3

Stage IV: any T, any N, M1

What are the 5-yr relative survival rates for breast cancer?

The 5-yr relative survival rates (observed survival in women with breast cancer vs. expected survival in women without breast cancer) according to the SEER registry of pts diagnosed 2003–2009

Localized (confined to primary site): 98.6%

Regional (spread to LNs): 84.4%

Distant (cancer has metastasized): 24.3%

TOXICITY

What are the acute and late toxicities of whole breast RT?

Acute toxicities: fatigue, dermatitis, hyperpigmentation, pneumonitis

Late toxicities: soft tissue fibrosis, telangiectasias, rib fractures, pulmonary fibrosis, cardiovascular Dz, 2nd RT-induced malignancy

What is the rate of acute skin breakdown, and where does it typically occur with whole breast RT?

25%–30% of pts experience skin breakdown, most often in the inframammary fold or axillary sulcus.

What % of women have a less than good or excellent cosmetic result after whole breast RT and lumpectomy?

20%–30% of pts have a more unfavorable cosmetic result.

In a pt with breast cancer, what is the rate of lymphedema after whole breast RT ± axillary LND? How does the RT technique affect risk?

15%–35% after RT + axillary LND; 5%–10% after RT and sentinel node Bx only. It is difficult to determine the RT effect b/c of other confounding tumor and Tx factors. However, retrospective studies suggest that tangent-only RT is associated with lower risk than directed nodal RT.

What is the RR of cardiovascular Dz death after RT to left-sided breast cancer compared to right-sided breast cancer?

Studies from the pre-3D planning era suggest that RT for left-sided breast cancer is associated with an RR of 1.5–2 for cardiovascular Dz death compared to RT for right-sided breast cancer. This has not been confirmed in women treated using modern RT techniques.

What is the risk of 2nd malignancy after whole breast RT?

The lifetime risk of 2nd malignancy after whole breast RT is 1%–2%.

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