Radiation Oncology: A Question-Based Review

General Breast Cancer

John P. Christodouleas and Richard C. Zellars

image 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

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

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

1.     Incidence: ~180,000 invasive breast cancers and ~65,000 noninvasive breast cancers annually.

2.     Mortality: ~40,000

What is median age of Dx for invasive breast cancer?

The median age for invasive breast cancer is 61 yrs.

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

1.     Highest Dx: whites

2.     Highest mortality: blacks

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.

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

The incidence of Dx was increasing.

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

The incidence of mortality was decreasing.

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

BRCA1 and BRCA2 are the most common mutations.

What ethnic ancestry is associated with the highest risk of carrying a BRCA1/BRCA2 mutation?

Ashknazi Jewish ancestry. As many as 1 in 40 Ashknazi Jews may have a BRCA1 or BRCA2 mutation.

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

Both BRCA1 and BRCA2 are associated with increased risk of ovarian cancer, but risks are higher with BRCA1 (40%–60% lifetime risk) compared to BRCA2 (10% lifetime risk).

How does familial breast cancer status and pt age affect breast tumor doubling time?

Pts with familial breast cancer and young age have a shorter tumor doubling time, so consider shortening screening intervals for these pts.

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 ones that increase or decrease the risk of breast cancer: younger age at menarche, younger age at menopause, nulliparity, prolonged breast-feeding, use of HRT.

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

2.     Decrease risk: younger age at menopause, prolonged breast-feeding

Estimate the annual risk of a contralat breast cancer in pts with a personal Hx of breast cancer.

1.     Premenopausal: 1%/yr

2.     Postmenopausal: 0.5%/yr

What is the definition of menopause?

1.     Menopause criteria for amenorrhea not related to Tx should include (a) bilat oophorectomy, (b) age ≥60 yrs, and (c) age <60 yrs and amenorrheic for ≥12 mos.

2.     If Tx-related amenorrhea, menopausal status must be maintained either from (a) oophorectomy or (b) serial measurements of FSH or estrogen at menopausal levels.

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

1.     For normal-risk women age 20–40 yrs: clinical breast exam every 1–3 yrs and periodic breast exam.

2.     For normal risk women age 40–49 yrs: recommendations are currently controversial, as the U.S. Preventive Services Task Force no longer recommends mammogram for this age group. However, the ACS and ACR still recommend mammograms every 1–2 yrs for this age group and annually for women age ≥50 yrs.

For a woman with prior RT exposure to the breast, when should screening begin for breast cancer and how?

Screening should begin 10 yrs after RT or at age 40 yrs, whichever comes 1st. Screen with an annual mammogram and clinical breast exams every 6–12 mos.

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

Per the American Cancer Society guidelines (2007), screen women who have ~20%–25% or greater lifetime risk of breast cancer based on 1 of many available risk models (e.g., Tyler J et al., Stat Med 2004). This does not include women with dense breast tissue.

According to NCCN 2010, what are the clinical indications and applications of dedicated breast MRI testing?

Clinical indications/application of dedicated breast MRI testing (NCCN 2010):

1.     Determine multifocality or multicentricity of Dz in the breast.

2.     Screening for contralat breast lesions in a newly diagnosed breast cancer pt.

3.     Breast cancer evaluation before and after neoadj therapy to define response to Tx and assess breast conservation therapy eligibility.

4.     To detect additional Dz in a mammographically dense breast.

5.     To detect primary Dz in pts with +axillary LNs with unknown primary or Paget Dz of the nipple.

6.     Since false+ findings on MRI are common, all lesions need to be sampled to r/o benign lesions.

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

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 analyzes a panel of 21 genes within a breast cancer tumor to estimate risk of any recurrence for early-stage, estrogen receptor (ER)+, node– breast cancer. NSABP B20 suggested that Oncotype DX may quantify benefit of chemo in this subgroup. The TAILORx trial is prospectively evaluating this hypothesis. Other genetic panels for women not eligible for Oncotype DX are being developed.

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.

image Workup/Staging

What is the workup for a breast lesion seen on mammogram?

Breast lesion workup: H&P (inquire about family Hx of breast and ovarian cancer, previous abnl mammogram, Hx of atypical ductal or lobular hyperplasia), CBC, CMP, bilat digital mammogram, spot compression views of abnl lesion, and stereotactic Bx of lesion

In a pt with T1-T2 breast cancer and a clinically– axilla, what is rate of pathologic axillary involvement?

The rate of pathologic axillary involvement is ~30%.

In a breast cancer pt with clinically+ axilla, what is chance that the axilla is negative upon dissection?

There is ~25% chance that the axilla is negative.

What are the 5 regional LN stations in breast cancer?

Regional LN stations in breast cancer:

1.     Station I: nodes inf/lat to pectoralis minor muscle

2.     Station II: nodes deep to pectoralis minor

3.     Station III: nodes sup/med to pectoralis minor

4.     Station IV: supraclavicular nodes

5.     Station V: internal mammary (IM) nodes

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

What is the AJCC T staging for invasive breast cancer according to the AJCC 7th edition (2009)?

1.     Tis: in situ (ductal CIS, lobular CIS, or isolated Paget)

2.     T1mi: microinvasion ≤1 mm

3.     T1a: >0.1–0.5 cm

4.     T1b: >0.5–1 cm

5.     T1c: >1–2 cm

6.     T2: >2–5 cm

7.     T3: >5 cm

8.     T4a: extension to chest wall, not including pectoralis muscle

9.     T4b: edema (including peau d–orange) or ulceration of skin of breast, or satellite nodules confined to same breast

10. T4c: both T4a and T4b

11. T4d: inflammatory 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 breast cancer to the dermis alone qualify as T4 Dz?

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

What is the AJCC clinical N staging for invasive breast cancer according to the AJCC 7th edition (2009)?

1.     N1: movable ipsi axillary LN

2.     N2a: ipsi axillary LNs fixed to one another

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

4.     N3a: ipsi infraclavicular LNs

5.     N3b: ipsi IM and axillary nodes

6.     N3c: ipsi supraclavicular nodes

What is the AJCC pathologic N staging for invasive breast cancer according to the AJCC 7th edition (2009)?

1.     pN(i–): negative by immunohistochemistry (IHC)

2.     pN(i+): positive by IHC only, but no cluster >0.2 mm (aka isolated tumor cell clusters)

3.     pN0(mol–): negative by RT-PCR

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

5.     pN1mi: all nodal mets >0.2 mm but <2 mm

6.     pN1a: 1–3 axillary LNs involved

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

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

9.     pN2a: 4–9 axillary LNs involved (tumor deposit at least >2.0 mm)

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

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

12. 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

13. pN3c: ipsi supraclavicular node

Define the AJCC breast cancer stage groupings using TNM status.

1.     Stage 0: Tis, N0

2.     Stage I: T1, N0

3.     Stage IIA: T2, N0 or T0-T1, N1

4.     Stage IIB: T3, N0 or T2, N1

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

6.     Stage IIIB: T4, N0-N2

7.     Stage IIIC: any T, N3

8.     Stage IV: any T, any N, M1

What are the 5-yr survival rates for the various stages of breast cancer?

The 5-yr survival rates according to the National Cancer Database of 211,645 pts diagnosed in 2001–2002:

1.     Tis (stage 0): 92.7%

2.     Stage I: 87.8%

3.     Stage IIA: 81.4%

4.     Stage IIB: 74.0%

5.     Stage IIIA: 66.7%

6.     Stage IIIB: 41.0%

7.     Stage IIIC: 49.3%

8.     Stage IV: 14.8%

(AJCC 7th ed., 2009)

image Toxicity

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

1.     Acute toxicities: fatigue, RT dermatitis, hyperpigmentation, pneumonitis

2.     Late toxicities: soft tissue fibrosis, telangiectasias, pulmonary fibrosis, precocious 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 5 yrs after whole breast RT +/+ axillary LND? How does the RT technique affect risk?

~15% after RT + axillary LND; ~5% 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 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%.