Radiation Oncology: A Question-Based Review

Early-Stage (I-II) Breast Cancer

Steven H. Lin and Richard C. Zellars

image Background

What histologic subtypes of IDC are associated with favorable outcomes?

Tubular, medullary, mucinous (colloid), and papillary

What are the classic histologic features of medullary carcinoma of the breast?

Medullary carcinoma of the breast shows a syncytial growth pattern of poorly differentiated tumor with a high mitotic rate. There is often a prominent lymphoplasmacytic reaction involving at least 75% of the periphery and present diffusely throughout the tumor. Medullary carcinoma of the breast is managed the same as IDC.

What is a phyllodes tumor of the breast?

Previously known as cystosarcoma phyllodes, phyllodes tumor ranges from benign to malignant and is a rare tumor with leaflike, lobulated appearance on microscopic section. It has both malignant epithelial and stromal components; the stromal component has the potential for metastatic spread. There is LN spread in 10% of cases, so there is a need for axillary dissection. Surgery is the preferred management. RT is used only for rare +margin and possibly large (>2 cm) tumors treated by breast conservation surgery (BCS).

What is Paget Dz of the breast? What is the clinical presentation?

Paget Dz of the breast is caused by malignant epithelial cells (Paget cells) infiltrating the epidermis through mammary ductal epithelium. The clinical presentation is crusting, scaling, itching, and redness on the skin of the nipple that can progress to ulceration and bleeding.

What % of Paget Dz is associated with an underlying breast cancer (invasive ductal carcinoma [IDC] or ductal carcinoma in situ [DCIS])?

>95% of Paget Dz is associated with underlying breast cancer, with 90% being IDC and 10% being DCIS.

What % of invasive cancers are lobular carcinomas?

5%–10% of invasive cancers are lobular carcinomas.

What % of lobular carcinomas are associated with contralat and synchronous primaries?

Up to 30% of lobular carcinomas are contralat synchronous and metachronous primary tumors.

Of the pts with early-stage breast cancers who will ultimately have recurrence, what % recurs after 5 yrs of follow-up?

According to the 25-yr follow-up of NSABP B04 (Fisher B et al., NEJM 2002), 25% of women fail distantly after 5 yrs, and 50% of women fail in the contralat breast. This supports the need for long-term follow-up.

According to the NSABP B04 trial, what % of women with a clinically– axilla were found to have axillary mets at LND?

Per NSABP B04, 40% of these women had axillary mets at LND.

Of the women who had a clinically– axilla and did not have a nodal dissection, what % eventually developed a clinically+ axilla?

20% of these women developed a clinically+ axilla.

image Workup/Staging

What is the size cutoff to be considered a microinvasive Dz in the primary breast tumor?

A primary breast tumor >0.1 cm is considered microinvasive Dz.

What is the workup for invasive breast cancer?

Invasive breast cancer workup: H&P (inquire about family Hx of breast or ovarian cancer, Hx of atypical ductal or lobular hyperplasia), CBC, CMP, bilat mammogram, estrogen receptor (ER)/progesterone receptor/HER2 status, and β-HCG (if premenopausal). If stage >IIA, then bone scan. Otherwise, imaging for suspicious Hx, physical, or lab findings.

List the subsets of stage I breast cancers (T1mic– T1a-c).

1.     T1mic: ≤ 0.1cm;

2.     T1a: >0.1 but ≤0.5 cm

3.     T1b: >0.5 cm but ≤1 cm

4.     T1c: >1 cm but ≤2 cm

All stage I tumors are node–.

What is the TNM staging for stage II breast cancers?

T2N0, T1-2N1, T3N0

T2 has tumors >2 cm but ≤5 cm; N1 has 1–3 +nodes. T3 has tumors >5 cm.

How are pN1(i+) and pN1mi defined for the involvement of breast cancer cells in the axillary LNs?

Based on the size of micrometastasis.

1.     pN1(i+): isolated tumor cells (ITCs) that are immunohistochemistry or hematoxylin and eosin (H&E) positive but ≤0.2 mm

2.     pN1mi: mets >0.2 mm and/or >200 cells but ≤2 mm

Are pN1(i+) counted for the total number of positive involved LNs?

No. ITCs in LNs are not excluded from a total +node count for purposes of N classification.

What % of breast cancer pts are diagnosed with stage I–II Dz?

~75% of breast cancer pts are diagnosed with stage I–II Dz. (Osteen RT & Karnell LH, Cancer 1994)

What is the T stage for Paget Dz of the breast?

The T stage for Paget Dz is Tis, but only if it is not associated with an underlying noninvasive (i.e., DCIS and/or lobular carcinoma in situ) or invasive cancers.

How should Paget Dz associated with an underlying breast cancer be staged?

Per the AJCC 7th edition (2009), Paget associated with underlying breast cancer should be staged according to the T stage of the underlying cancer (Tis, T1, etc.).

image Treatment/Prognosis

What are the management options for early-stage breast cancers?

Early-stage breast cancer management options:

1.     Modified radical mastectomy +/− chemo +/− RT

2.     Breast conservation therapy (BCT = BCS + RT) +/− chemo

Consider endocrine therapy for all women with ER+ tumors (even for T1a tumors) for risk reduction and to diminish the small risk of Dz recurrence.

When should adj chemo be utilized in the management of early-stage breast cancers?

Adj chemo is recommended for tumors > 1 cm and T1b tumors that are ER– +/− HER2. As well, it can be considered for 0.6–1-cm tumors that are grade 2 or 3 or + LVI. For ER+ tumors with ≥T1c Dz (including T2–T3), consider using Oncotype DX to determine the risk score for the benefit of chemo. However, the benefits of chemo are not certain for pts >70 yrs of age.

What systemic therapy is recommended for pts with ER+ tumors that are <1 cm?

Endocrine therapy would be the recommended systemic therapy without chemo.

What are some general principles of administering adj endocrine therapy?

General principles for administration of adj endocrine therapy:

1.     If the pt is premenopausal, tamoxifen (20 mg/day) is given for 5 yrs. If the pt remains premenopausal, therapy ends. However, if the pt becomes postmenopausal, aromatase inhibitors (AIs) × 5 yrs are added.

2.     If the pt is postmenopausal, AI × 5 yrs or tamoxifen × 2–3 yrs or 4.5–6 yrs → AI × 5 yrs is recommended.

3.     Tamoxifen × 5 yrs is given for any pts who are intolerant, refuse, or have contraindications for AIs. (NCCN 2010)

What are the contraindications for the use of AIs?

Premenopausal status or the use of HRT in postmenopausal women

What are the major side effects of tamoxifen and AIs?

1.     Tamoxifen: small increase in blood clots, strokes, uterine cancer, and cataracts

2.     Aromatase inhibitors: bone loss and osteoporosis, joint pain and stiffness, and hypercholesterolemia. Bone mineral density should be monitored. Consider bisphosphonates or statin drugs to counter the effects.

When should paclitaxel (T) be added to Adriamycin/cyclophosphamide (AC) chemo?

T should be added for node+ pts. AC × 4 cycles can be used alone for >1 cm, –node tumors. AC followed by T should be administered in a dose-dense fashion (q2wks), or AC q3wks → weekly T × 12 wks.

Drug doses: Adr, 60 mg/m2 intravenously day 1; cyclophosphamide, 600 mg/m2 intravenously day 1; T, 175–225 mg/m2 by 3-hr intravenous infusion day 1 q21days, or 80 mg/m2 by 1-hr intravenous infusion weekly × 12 wks.

What systemic therapies are recommended for HER2+ tumors?

Systemic therapies for HER+ tumors:

1.     If the tumor is <5 mm and a –node, just give endocrine therapy (if ER+).

2.     If the tumor is 0.6–1 cm and a –node, consider combination chemo +/− trastuzumab (Herceptin).

3.     If the tumor is >1 cm, add combination chemo with Herceptin.

4.     Combination chemo + Herceptin is recommended for all node+ pts. The preferred combination chemo with Herceptin is Taxotere/carboplatin/Herceptin (TCH): Taxotere (75 mg/m2 intravenously day 1), carboplatin (AUC 6 intravenously day 1), q21days × 6 cycles, and Herceptin (4 mg/kg on wk 1 → 2 mg/kg × 17 wks → 6 mg/kg q3wks until 1 yr elapses). B/c of synergistic cardiotoxicity of traditional AC-TH, TCH is preferred.

How should trastuzumab (Herceptin) be used in the management of early-stage breast cancers?

Trastuzumab can be used in pts with HER2tumors > 1 cm. T1a-T1b tumors that are node– have a good prognosis even with HER2 amplification. This cohort is not well studied in randomized trials; therefore, the potential long-term cardiac morbidity risks with uncertain Dz control benefits should be weighed before using trastuzumab.

If trastuzumab is added to the Tx of BCT for early-stage breast cancers, how is it administered?

Trastuzumab is added after completion of Adr-based chemo, but it can be administered with Taxol or Taxotere at 4 mg/kg with the 1st dose of Taxol. Trastuzumab is given on a weekly basis (2 mg/kg) for 1 yr and can be given concurrently with RT. If capecitabine is added as an RT sensitizer, trastuzumab can also be given concurrently.

What data supports BCT (lumpectomy + radiotherapy) having equivalent survival outcomes to mastectomy +/+ LND?

Several large randomized trials (NSABP B06, Milan III, Ontario, Royal Marsdan, EORTC 10801) support this, but B06 has the longest (20-yr) follow-up data. Recent Oxford meta-analysis summarizes the data and survival outcomes:

1.     NSABP B06 (Fisher et al., NEJM 2002): 1,851 stage I–II pts randomized to (a) total mastectomy, (b) lumpectomy alone, or (c) lumpectomy + RT (50 Gy). 20-yr follow-up results showed that there was no difference in DFS, OS, or DM. The 20-yr ipsilateral breast tumor recurrence (IBTR) rate was 14% with BCS + RT vs. 39% in BCS alone (25% absolute risk reduction).

2.     EBCTCG Oxford meta-analysis (EBCTCG Collaborators, Lancet 2005): 7,300 women enrolled in 10 trials for BCS +/− RT. The 5-yr LR risk reduction was 19% (7% in RT vs. 26% in BCS alone). The 15-yr breast cancer mortality was reduced by 5.4% (30.5% vs. 35.9%) with RT. The 15-yr overall mortality risk was reduced by 5.3% (35.2% vs. 40.5%), all highly significant (p = 0.005). So for every 4 women prevented to have LR, 1 woman is saved (4:1 ratio).

What % of pts are eligible for BCT for early-stage breast cancers ?

In early-stage breast cancers, 75%–80% of pts are eligible for BCT. (Morrow M et al., Cancer 2006)

What is the relative rate of BCT for invasive lobular carcinoma (ILC) compared with IDC?

The rate of breast conservation is lower for ILC than IDC due to the propensity for multifocality (Fisher ER et al., Cancer 1975). The rate is ~75% vs. ~80% for IDC (Morrow M et al., Cancer 2006).

What are some absolute contraindications for BCT for pts with early-stage breast cancer?

Absolute contraindications for BCT in early-stage breast cancer:

1.     Prior RT exposure

2.     Multicentricity

3.     Diffuse microcalcifications

4.     1st or 2nd trimester of pregnancy

5.     Persistently +margin

(Note: The 1st 4 contraindications are from BCT guidelines: Winchester DP & Cox JD, CA Cancer J Clin 1992.)

What are some relative contraindications for BCT in pts with early-stage breast cancer?

Relative contraindications for BCT in early-stage breast cancer:

1.     Ratio of tumor to breast size (suboptimal cosmetic outcome)

2.     Locally advanced Dz (but can consider BCT for larger tumors after neoadj chemo)

3.     Collagen vascular Dz (especially scleroderma, mixed connective tissue Dz, or CREST syndrome (Calcinosis, Raynaud, Esophageal dysfunction, Sclerodactyly, Telangiectasia)

4.     Pregnancy (can possibly delay RT until after delivery)

Is nodal involvement a contraindication for BCT?

No. The extent of nodal involvement may only affect the extent of nodal irradiation, though this is still controversial. With between 1 and 3 nodes, consider breast and axillary irradiation. If >4 nodes are involved, consider comprehensive nodal irradiation.

Is there a contraindication for BCT in pts with a positive family Hx of breast cancer?

No. There is no evidence that demonstrates increased ipsi or contralat breast cancers in pts with a positive family Hx after BCT. (Vlastos G et al., Ann Surg Oncol 2007)

Are BRCA mutations a contraindication for BCT?

No. Though Pierce LJ et al. reported that the IBTR rate may be higher in BRCA1/BRCA2 mutation carriers compared to wild-type individuals (HR 1.99, p = 0.04), this difference becomes indistinguishable after oophorectomy in BRCA carriers. Contralateral breast tumor recurrence (CBTR) is also much higher (10-yr/15-yr recurrence risk is 26%/39% in carriers vs. 3%/7% in wild-type individuals) and is substantially reduced with tamoxifen (HR 0.31) or tamoxifen + oophorectomy (HR 0.13). However, the CBTR rate is still significantly higher in mutation carriers treated with oophorectomy compared to controls. (JCO 2006)

What is the typical whole breast RT dose, and what data supports the use of a tumor bed boost?

1.     Typically, the dose is 45–50 Gy to the whole breast. EORTC and French studies have demonstrated an improved LR rate with a 10–16 Gy boost.

2.     EORTC boost trial (Bartelink et al., JCO 2007): 5,318 women with BCT, 10-yr update: 50 Gy vs. 50 Gy + 16 Gy boost (surgical margin [SM]–) or + 26 Gy boost (SM+). 10-yr LF: 6.2% + boost vs. 10.2% − boost. Absolute benefit was greatest in women <50 b/c they have a higher risk of LR (24% − boost vs. 13.5% + boost for women <40 yo), but proportional benefits were seen across all age groups.

3.     Lyon boost trial (Romestaing et al., JCO 1997): 1,024 pts, 50 Gy vs. 50 Gy + 10 Gy boost. At 3-yr follow-up, LF was reduced in the boost arm (3.6% vs. 4.5%).

4.     In general, a boost of 10–16 Gy should be considered for pts at higher risk for LR (age <50 yrs, positive axillary nodes, +LVI, or close SMs). This can be administered with brachytherapy, electrons, or external photons.

Is there a need for a higher tumor boost dose in pts with incomplete tumor excision after BCS?

No. In the EORTC boost trial, 251 pts with microscopically incomplete tumor excision were randomized to low (10 Gy) vs. high (26 Gy) boost. With median follow-up of 11.3 yrs, there was no difference in LC or survival. There was significantly more fibrosis in the high-dose arm. (Poortmans PM et al., Radiother Oncol 2009)

Can RT be used in the Tx of axillary nodes in place of surgery if axillary nodal dissection is not performed?

1.     Possibly. This is based on the results of NSABP B04.

2.     NSABP B04 (Fisher B et al., NEJM 2002): randomized trial in 2 subsets of pts. Subset 1 included 1,079 pts with clinically– nodes randomized to 3 arms: (a) radical mastectomy, (b) simple mastectomy alone (+ axillary nodal dissection if clinically+ later), and (c) simple mastectomy + nodal RT. Subset 2 included 586 pts with clinically+ nodes randomized to 2 arms: (a) radical mastectomy vs. (b) simple mastectomy − axillary dissection but postop RT; no adj chemo.

3.     Results: At 25-yr follow-up, there were no differences in LF, DFS, or OS in any of the groups.

4.     Caveat: Approximately one third of pts who should not have had a nodal dissection had some nodes removed. Thus, the results of the study may be questioned.

What is the next step in the management for a pt who undergoes a lumpectomy with a focal +margin?

This is controversial. Most would advocate taking the pt back to surgery for re-excision, which may diminish the 10-yr risk of LR to baseline levels (initial SM–: 7%, SM+: 12%; SM close: 14%; re-excision SM–: 7%, re-excision persistent SM+: 13%, re-excision persistent SM close: 21%). (Freedman G et al., IJROBP 1999)

Is there a subset of women whose LR risk may not be substantially influenced by margin positivity after BCS?

Possibly. There are data to suggest that the effect of margin positivity on LR may be dependent on age <40 yrs. In an analysis of 1,752 pts, 193 were SM+. Overall 10-yr LRR was 6.9% (SM–) vs. 12.2% (SM+). 5-yr LRR for pts ≤40 yo was 8.4% (SM–) and 37% (SM+) (p = 0.005); for pts >40 yo, the LRR was 2.6% (SM–) and 2.2% (SM+). (Jobsen JJ et al., IJROBP 2003)

Should women with T1-2N0 invasive breast cancer treated with mastectomy to a +margin be treated with adj RT to the chest wall (CW) as well?

In a British Columbia retrospective study (Truong PT et al., IJROBP 2004), out of 2,570 women with early-stage breast cancer treated with mastectomy, 94 pts had a +margin. About half (41 pts) were treated with postmastectomy radiation therapy (PMRT). B/c of the small numbers, there was a trend to improvement with PMRT in pts >50 yrs, T2 tumor, grade III, and LVI. In pts without these features, there was no LR without PMRT.

Which is a more important factor to determine LR, margin status, or node positivity?

Margin status is more important to determine LR, whereas nodal positivity is more predictive of distant recurrence and OS. Margin status in relation to LR may be related to nodal positivity. Besana-Ciani I & Greenall MJ (Int Semin Surg Oncol 2008) showed that in 773 pts treated with BCT, LR was 12% in SM– vs. 28% in SM+ node– pts, but LR was equivalent (12% and 18%) in node+ pts. This may be due to the fact that margin status in node+ pts does not dictate prognosis as much as in node− pts.

What is EIC, and does it have prognostic significance in the recurrence risk of pts treated with BCT?

1.     EIC (extensive intraductal component) is defined as DCIS comprising 25% of the tumor mass with DCIS and foci of DCIS separate from the invasive Dz. DCIS with focal microinvasive Dz areas of invasion also fits this category.

2.     Yes, but it is largely dependent on SM status. From studies mainly out of JCRT, EIC is only prognostic for LF if the margin status is considered. If there is a close or +margin, EIC is associated with a high risk of recurrence. (Gage I et al., Cancer 1996)

What data suggests that results of BCT can be further improved with the use of tamoxifen?

NSABP B21 (Fisher B et al., JCO 2002): 1,009 pts with ≤1-cm tumors s/p lumpectomy randomized to 3 arms: (a) tamoxifen alone (10 mg bid × 5 yrs), (b) RT alone (50 Gy), and (c) RT + tamoxifen. After 8-yr follow-up, the IBTR was 16.5% with tamoxifen alone vs. 9.3% with RT alone vs. 2.8% with RT + tamoxifen. There was no difference in OS. No benefit was seen in ER– tumors. CBTR was 0.9%, 4.2%, and 3.0% in the 3 arms, respectively.

Are there pt subgroups with a low risk of LR who can be treated with BCS and systemic therapy alone without RT?

Possibly. 2 recent trials have been conducted to answer the question whether age is a determining factor. The data suggests that the risk is very low only for pts >70 yo and possibly in those with very small tumors ( <1 cm), so a discussion can be made about withholding RT if the pt is being treated with tamoxifen. There is no data whether the same applies for AIs.

Princess Margaret Hospital/Canadian trial (Fyles AW et al., NEJM 2004): 769 women ≥50 yo (median age 68 yrs) with T1 or T2 (≤5 cm) –nodes (in women age ≥65 yrs, either clinical or pathologic evaluation was sufficient and sentinal lymph node [SLN] Bx was not routinely done) underwent lumpectomy to –margins and were randomized to (a) tamoxifen alone (20 mg/day × 5 yrs) vs. (b) tamoxifen + RT (40 Gy in 16 fx with a boost of 12.5 Gy in 5 fx). After 8-yrs follow-up, RT reduced LR from 17.6% to 3.5%. But with tumors <1 cm, the risk of relapse was 2.6% vs. 0% for the RT group (p = 0.02). In those >60 yo with <1 cm tumor, the risk was no different between the 2 arms (1.2% vs. 0%), but this was unplanned analysis with a short follow-up.

Intergroup trial (Hughes KS et al., NEJM 2004): 636 women ≥70 yo with T1, clinically N0, ER+ tumors were randomized to tamoxifen vs. tamoxifen + RT after lumpectomy to –margins. Node status was assessed clinically only, and axillary dissection was discouraged. RT was 45 Gy to the whole breast with a boost of 14 Gy. The initial 5-yr LF rate was 4% vs. 1%, respectively. At 8-yr follow-up, the LF rate in the tamoxifen alone arm was 7% vs. 1% in RT.

What are some alternative fractionation regimens for whole breast irradiation as part of BCT? What 2 RT regimens can be employed for use in BCT?

Traditionally in the U.S., alternative fractionation regimens include conventional fractionation at 1.8–2 Gy/fx to 45–50 Gy whole breast → a boost to 60–66 Gy. However, several recent published trials suggest the same outcomes using a hypofractionated approach.

Canadian regimen (Whelan TJ et al., JNCI 2002; Whelan TJ et al., NEJM 2010): RCT using 42.5 Gy in 16 fx (2.65 Gy/fx) vs. 50 Gy in 25 fx (2 Gy/fx) with no boost; 1,234 T1-2N0 pts, all with –SMs. Women with > 25-cm breast width were excluded (to reduce heterogeneity of dose to the breast). At median follow-up of 69 mos, there was no difference in LC, OS, or cosmesis. Updated 10-yr follow-up: there was no difference in DFS or cosmesis. LR risk was 6.7% in the standard regimen vs. 6.2% in the hypofractionated regimen. Good to excellent cosmesis was equivalent (71.3% standard vs. 69.8% hypofractionated).

British regimen (START B trials, Lancet 2008): 2,215 women with pT1-3N0-1 s/p surgery randomized to 50 Gy in 25 fx vs. 40 Gy in 15 fx (2.67 Gy/fx) with no boost given in either arm. After 6-yr follow-up, there was no difference in IBTR (3% vs. 2%). Late adverse events were not greater in the 40-Gy arm (if not a bit better).

How should chemo be sequenced with radiotherapy after BCS?

JCRT sequencing trial (“Upfront-Outback” trial) (Bellon et al., JCO 2005): per the initial report (Recht et al., NEJM 1996), the 5-yr crude rate of distant recurrence was better in the chemo 1st arm (20% vs. 32%). However, in the 11-yr follow-up update, there was no difference in DFS, LR, DM, or OS. For those with a –margin, the crude LR rate was 6% in the chemo 1st arm vs. 13% in the RT 1st arm. However, the study was not powered to show any differences.

Thus, either sequence is acceptable. However, convention is to give chemo 1st.

What is the max length of time that RT can be delayed after BCS before impacting clinical outcomes?

Generally, RT can start whenever the pt is finished healing, which can range from 2-4 weeks, but possibly no more than 20 wks. There is recent data to suggest that if there is a delay >20 wks in pts who rcv chemo, the DFS and breast cancer mortality rates increase (British Columbia study: Olivotto IA et al., JCO 2009).

Can accelerated partial breast irradiation (PBI) be considered an option for BCT?

As of 2010, this is not an option. This is a clinical question being tested in the NSABP B39/RTOG 0413 trial, which randomizes women to whole breast RT vs. PBI by 3 methods (interstitial, mammosite, and EBRT).

ASTRO has published guidelines on who may be considered for PBI off trial (Smith BD et al., IJROBP 2009). Generally, pts considered “suitable” are >60 yo, ER+, IDC ≤2 cm (no DCIS or ILC), N0 (nor pN[i+]), unicentric, ≥2-mm margin, no LVSI, no EIC, and BRCA1/BRCA2–. Several retrospective studies have demonstrated excellent LC in pts with short follow-up (Smith BD et al., IJROBP 2009).

What are the doses recommended for PBI if done off protocol?

For EBRT38.5 Gy in 10 fx using 3D-CRT. For brachytherapy (interstitial or intracavitary forms), the dose is 34 Gy in 10 fx.

The target includes the tumor bed and a 1-cm margin for brachytherapy and a 1–1.5 cm for EBRT to account for uncertainties in setup due to respiration.

Are there subsets of women who undergo mastectomy for early-stage breast cancers (T1-2N0) who may benefit from PMRT?

Yes. PMRT is generally recommended (NCCN, ASCO) in women with T3-4N+ (>4 nodes) Dz according to PMRT RCTs (Chapter 45). PMRT may not be necessary if the margins are clear (≥1 cm). However, consider PMRT for those with SMs <1 mm.

In pts treated with mastectomy for early-stage cancer, Vancouver retrospective data suggest that PMRT may also benefit women with certain risk features (LVSI, grade 3, no chemo, or T2 tumors). In the presence of 2–3 factors (LVSI + grade 3 or grade 3 + T2 + no chemo), the LRR risk is ~21%–23% without RT. (Truong PT et al., IJROBP 2005)

In a separate report from Harvard (Jagsi R et al., IJROBP 2005), similar factors predicted for LRR after mastectomy without PMRT (close margin, ≥T2, premenopausal pt, and LVI). 10-yr LRR (80% in the CW) according to risk factors was 0, 1.2%; 1, 10%; 2, 18%; 3, 41%.

How should a Dx of breast cancer be managed in a pregnant woman?

1.     Depends on the stage of pregnancy. Generally, adj chemo can be used, though not during the 1st trimester of pregnancy. RT or hormones should be added postpartum. Chemo used during pregnancy utilizes combinations of Adr, cyclophosphamide, and 5-FU.

2.     1st trimester: consider termination. If the pt refuses, consider mastectomy + axillary staging. If chemo is needed, add it during the 2nd trimester. Adj RT and hormones, if needed, should be added postpartum

3.     2nd–3rd trimester: BCT or mastectomy can be considered. Neoadj chemo can be considered. Surgical management and chemo in pregnant women is the same as that used in nonpregnant women, but adj hormones and RT cannot be added until the postpartum period.

(Adopted from NCCN 2010)

image Toxicity

What is the typical recommended follow-up schedule for pts treated for invasive breast cancer?

Invasive breast cancer recommended follow-up after Tx:

1.     Interval H&P q4–6mos × 5 yrs, then annually

2.     Mammogram annually for contralat breast, q6–12mos for ipsi breast (if conserved)

3.     Annual gynecologic exam for women with intact uterus on tamoxifen

4.     Bone health assessment (bone mineral density scan) at baseline and periodically during course of use of AIs

For pts who have large breasts with large medial to lat separation (>22–24 cm), what techniques will improve dose homogeneity?

Photon energy > 10 MV to keep max inhomogeneity <10% and field segmentation techniques (IMRT). Avoid medial wedges to reduce scatter to contralat breast in pts <45 yo.

Which randomized trial demonstrated the superiority of 3D-IMRT compared to 2D tx approaches for minimizing cosmetic changes to the breast?

Royal Marsden (Donovan E et al., Radiother Oncol 2007) randomized 306 women to 2D-RT or 3D-IMRT. RT was 50 Gy → boost to 11.1 Gy with electrons. There was a significant cosmetic difference in the breast of 2D-RT (58%) vs. 3D-IMRT (40%) pts. Fewer pts in the IMRT group developed palpable induration. There were no differences in the QOL between the groups. A randomized trial (Pignol JP et al., JCO 2008) comparing breast IMRT to standard techniques showed IMRT to be superior with respect to moist desquamation (31% vs. 48%) and improved dose distribution.

What is the risk of 2nd malignancies in pts treated for early breast cancer with RT?

From the WECARE study (Stovall M et al., IJROBP 2008), women <40 yo receiving >1 Gy to the contralat breast had an RR of 3. However, this excessive risk was not seen in pts >40 yo. Sarcomas (mostly angiosarcomas) within the RT field were <1% (~10 cases in 10,000) within 10–30 yrs. (Taghian A et al., IJROBP 1991; Yap J et al., IJROBP 2002; Kirova YM et al., Cancer 2005)

What is the risk of lymphedema in pts treated for breast cancer?

The risk is low ( <5%) if lymphedema is treated with RT alone, SLN Bx alone, or level I–II axillary dissection. A complete axillary dissection increases the rate to ~10%. Comprehensive nodal RT with axillary dissection further increases the risk to >15%. (Refer to a review by Erickson VS et al., JNCI 2001.)

What is the risk of brachial plexopathy for a pt treated for breast cancer?

Median time to developing brachial plexopathy is ~10–12 mos (range 1.5–77 mos). It is highly dependent on fractional dose and total dose administered. Hypofractionated doses 2.2–4.6 Gy and total doses from 43.5–60 Gy can increase plexopathy from 1.7%–73% (normally <1%). (Galecki J et al., Acta Oncol 2006)

According to JCRT data (Pierce SM et al., IJROBP 1992), if dose is kept at <50 Gy, the risk is <1% without chemo and ~4.5% with chemo. If the dose is above 50 Gy, the risk is 5.6% (but 1.3% if <50 Gy).

What is the risk of pulmonary toxicities, such as lung fibrosis and symptomatic pneumonitis, after BCT for breast cancer?

Pulmonary fibrosis occurs in everyone on imaging in the treated pleura, but clinical pneumonitis is rare (1%) that occurs as chronic cough, fever, nonspecific infiltrate on CXR 3–9 mos after RT. The rate may be influenced by systemic therapy.

What is the long-term risk of fibrosis in the treated breast after BCT, and what are the predictors for breast fibrosis?

Cosmesis was poorer in the boost arm in the EORTC boost trial (3-yr excellent/good cosmesis: 86% [no boost] vs. 71% [+boost], SS) (Vrieling C et al., IJROBP 1999). The risk of fibrosis significantly increased with max whole breast dose + concomitant chemo and postop breast edema/hematoma, but it decreased if whole breast RT was given with >6 MV photons (Collette S et al., Eur J Cancer 2008).