Radiation Oncology: A Question-Based Review

Locally Advanced Breast Cancer

Owen C. Thomas and Tse-Kuan Yu

image Background

What is locally advanced breast cancer (LABC)?

Typically, the term refers to stage III Dz (T3N1, N2-N3, or T4). However, stage IIB pts with T3N0 Dz may be included. Inflammatory breast cancers (IBCs) are included, but metastatic Dz is not. LABC can be separated into those cancers that are operable and those that are not.

What is the meaning of LABC historically?

LABC refers to those breast cancers that demonstrate poor outcomes when managed surgically. Haagensen & Stout (Ann Surg 1943) published an analysis of 1,135 pts treated with radical mastectomy alone. This analysis revealed 5 “grave signs” of LABC and an understanding of the limited efficacy of mastectomy alone in managing locally advanced pts.

What are the 5 grave signs of LABC as defined by Haagensen & Stout?

Grave signs of LABC (per Haagensen & Stout):

1.     Limited edema of skin or “peau d–orange” appearance

2.     Ulceration of skin

3.     Fixation of tumor to chest wall (CW)

4.     Axillary LNs ≥2.5 cm

5.     Fixation of axillary LN

What are the epidemiologic trends and incidence of LABC?

The incidence of T3-T4 Dz decreased by 27% from 1980–1987 (coincident with the institution of mammography.) Analysis of the SEER database from 1992–1999 indicated that LABC (stage III other than IBC) and IBC made up 4.6% and 1.3% of all female breast carcinomas.

What is the distinct prognosis of IBC compared to other pts with LABC?

Pts with IBC have twice the risk of death compared to other pts with LABC.

What is the prevalence of IBC?

1%–4% of breast cancer cases are IBC.

Is LABC more common among certain ethnic groups?

Yes. A higher proportion of black women have LABC.

What are the histologic subtypes of LABC?

The histologic subtypes are the same for LABC as for earlier-stage Dz. Infiltrating ductal carcinoma is still the most common, but favorable histologies, such as tubular, medullary, and mucinous, are less frequently represented.

Are there genetic/molecular factors associated with LABC?

No. There are no molecular markers that define LABC. However, tumors with HER2/Neu positivity, BRCA1 mutation, and triple-negative (estrogen receptor [ER]–, progesterone receptor [PR]–, HER2–) are associated with aggressive phenotypes. A genomic profile of basal and HER2 subtypes is associated with a poor prognosis as well. The use of Herceptin in HER2+ positive tumors has improved their outcome, though.

image Workup/Staging

What is the workup for locally advanced invasive breast cancer?

Invasive breast cancer workup: H&P, CBC, liver profile, ER/PR/HER2 status; diagnostic mammogram and US as necessary; bone scan, CXR (CT chest optional), and CT abdomen; US or MRI abdomen as needed

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

In T2-T3 pts with a clinically– axilla, there is pathologic axillary involvement in ~30%.

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

In pts with a clinically+ axilla, there is a ~25% chance for a negative axilla upon resection.

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

2.     Station II: nodes deep to pectoralis minor

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

4.     Station IV: supraclavicular nodes

5.     Station V: internal mammary (IM) nodes

“Infraclavicular” nodes typically refers to the level III axillary nodes by radiation oncology.

How is IBC diagnosed?

IBC is a clinical Dx, with characteristics of rapid onset (<3 mos), generalized induration, often without an associated mass (classic type), peau d–orange appearance, and a diffuse skin erythema affecting more than two thirds of the breast. Enlargement, flattening and retraction of the nipple with warmth, and tenderness are common. IBC is characterized pathologically by cancer cells in dermal lymphatics (not necessary for Dx). Random Bx of breast parenchyma may yield cancer cells.

image Treatment/Prognosis

What are the most important factors that predict for LRR?

Increasing number of LNs with Dz and breast tumor size are the most important factors that predict for LRR.

What are the basic principles of treating LABC?

1.     Inoperable LABC: neoadj chemo is used to shrink the tumor and potentially convert it to be operable. Neoadj or adj chemo should be included.

2.     Operable LABC: Neoadj or adj chemo are used. Modified radical mastectomy (including level I–II axillary LNs) is the definitive locoregional Tx. PMRT is indicated in most circumstances. Hormonal therapy and Herceptin are incorporated as appropriate per receptor status of Dz.

What is a Halsted radical mastectomy?

Halsted radical mastectomy includes resection of all breast parenchyma, a large portion of breast skin, and major and minor pectoral muscles en bloc with axillary LNs.

What is spared with a modified radical mastectomy?

Modified radical mastectomy spares the pectoralis muscle.

What is spared with a total or simple mastectomy?

In a total or simple mastectomy, only the breast tissue is removed with overlying skin. Axillary LNs are not dissected.

What is considered an “adequate” axillary LND for purposes of staging and clearance?

Oncologic resection of levels I–II is considered standard and adequate. The LNs and axillary fat pad need to be removed en bloc. If suspicious nodes are present in level III, then level III dissection should be performed.

What is standard systemic chemo?

Standard chemo at present includes an anthracycline- and taxane-based regimen (e.g., Adriamycin/cyclophosphamide [AC] and Taxol).

What is meant by “dose-dense” chemo?

Dose-dense chemo is administered q2wks as opposed to q3wks.

Has dose-dense chemo been demonstrated to be superior in a prospective randomized trial?

Yes. Intergroup trial C9741 randomized 2,005 node+ pts to AC × 4 > Taxol × 4 given q3wks vs. q2wks. 4-yr DFS improved from 75% to 82% with the q2wk schedule. The risk ratio for OS was 0.69 in favor of the q2wk schedule. Median follow-up was 36 mos. Severe neutropenia was also less frequent with the dose-dense schedule.

What is the rationale for the use of neoadj chemo for LABC?

Neoadj chemo may convert pts with unresectable LABC to resectability. It may also be used to shrink large breast tumor requiring mastectomy in resectable pts to be managed with breast conservation surgery (BCS). Neoadj trials have the advantage of providing pathologic assessment of chemo response at the time of surgery. If the tumor is not responsive to 1 chemo regimen and progresses clinically, a different chemo regimen can be used.

What major study determined whether neoadj chemo improves survival compared to adj chemo in LABC?

NSABP B18 was designed to assess whether preop AC resulted in improved DFS and OS compared to postop AC. Secondary aims were to assess response to preop AC and correlate with survival and LR outcomes. Rates of BCS were also assessed. All women were deemed operable at enrollment, and the majority had T2 or smaller primary and clinically node– Dz. At the most recent follow-up (16 yrs) (Rastogi et al., JCO 2008), there has been no significant difference in OS or DFS between the women treated with neoadj vs. adj chemo. There is a trend, however, for women <50 yo for improved DFS and OS when treated preoperatively (p = 0.09 and 0.06). There was a 27% conversion rate from mastectomy to BCS.

What procedures should be done prior to starting neoadj chemo for LABC?

Core Bx and wire localization for the Bx bed (in case the pt has a CR to chemo). Perform sentinal lymph node (SLN) Bx if cN0; if cN+, consider FNA Bx.

Does adding Taxol to standard AC chemo improve the outcomes of pts with breast cancer?

Yes. Adding Taxol improves response rates, DFS, and OS.

NSABP 27 randomized operable pts to preop AC, preop AC + Taxol, or preop AC + postop Taxol. Here, the addition of Taxol did not improve survival outcomes but did improve pCR in the preop group (26% vs. 13%). (Rastogi et al., JCO 2008)

The CALGB 9344 study randomized 3,121 operable pts with LN+ Dz and found that adding Taxol q3wks × 4 to AC × 4 improved DFS and OS. (Henderson IC et al., JCO 2003)

In a retrospective study of 1,500 pts on CALGB 9344, the benefit of Taxol appeared to be in HER2+ tumors and not HER2−/ER+ tumors. (Hayes DF et al., NEJM 2007)

ECOG E1199 randomized 4,950 stage II–IIIA breast cancer pts to AC q3wks × 4 → Taxol q3wks × 4, AC q3wks × 4 → Taxol × 12 weekly, AC q3wks × 4 → Taxotere q3wks × 4, and AC q3wks × 4 → Taxotere × 12 weekly. The weekly Taxol arm had improved DFS (HR 1.27) and OS (HR 1.32). The effect was significant in all pts, including those with ER+/HER2− tumors. (Sparano JA et al., NEJM 2008)

In NSABP 18 and 27, did pCR at the time of surgery correlate with good OS and DFS outcomes?

Yes. In both NSABP 18 and NSABP 27, pCR at the time of surgery correlated with improved OS and DFS compared to non-pCR pts.

What other seminal neoadj chemo trials addressed neoadj vs. adj chemo and its role regarding BCS?

EORTC 10902 randomized 698 pts with early breast cancer to preop vs. postop chemo (5-FU/epirubicin/cyclophosphamide × 4). Endpoints were BCS, DFS, OS, and tumor response. At 10-yr follow-up, there was no difference in OS or LRR. Neoadj chemo was associated with an improved rate of BCS. (Van der Hage JA et al., J Clin Oncol 2001)

In EORTC 10902, was there a difference in the # of BCS between arms? Was there a difference in outcomes between planned breast-conserved pts and breast-converted pts?

BCS increased from 22% to 35% in the preop chemo arm. While the initial follow-up of EORTC 10902 indicated that converted breast-conserved pts did worse in terms of OS compared to planned pts—an indication that prechemo staging remains relevant. However, the most recent 10-yr follow-up data indicate that there is no difference in survival outcomes between these 2 groups. (Van der Hage JA et al., J Clin Oncol 2001)

Postmastectomy radiation therapy (PMRT) was the standard of care for many decades. Why did it fall out of favor?

There have been more than 25 prospective randomized trials evaluating PMRT over more than 50 yrs. Historically, PMRT was typically offered since pts presented at later stages and no chemo was given. Historical series, while uniformly demonstrating improved LC, did not demonstrate survival benefit.

Meta-analysis by Stjernsward (6 trials) demonstrated a 1%–10% decrease in OS with PRMT. (Lancet 1974)

Meta-analysis by Cuzick et al. (9 trials) demonstrated no OS survival benefit with PMRT at 10 yrs. (Cancer Treat Rep 1987)

An update by Cuzik demonstrated that PMRT increased cardiac mortality and slightly decreased breast cancer mortality. (J Clin Oncol 1994)

Therefore, with the addition of chemo (i.e., cyclophosphamide/methotrexate/5-FU [CMF]), PMRT went out of favor at the publication of the meta-analysis studies.

What are some criticisms of older PMRT data and meta-analysis?

Criticisms of older PMRT data include the significant heterogeneity of surgical and RT techniques, old RT techniques with associated cardiac and pulmonary toxicity, and lack of systemic therapy, implying that clinically undetectable systemic Dz was not well controlled.

What 3 randomized prospective trials are considered to represent the “modern” PMRT experience?

The Premenopausal Danish Trial (DBCG 82b) (Overgaard et al., NEJM 1997), the Postmenopausal Danish Trial (DBCG 82c) (Overgaard et al., Lancet 1999), and the British Columbia PMRT Trial (Ragaz et al., JNCI 2005) represent the “modern” PMRT experience.

What were the design and study outcomes of Premenopausal Danish Trial DBCG 82b?

In Premenopausal Danish Trial 82b, 1,708 women were randomized to mastectomy and adj CMF + chemo (8 cycles) or − RT (9 cycles). Inclusion criteria were +axillary LN, tumor >5 cm, or involvement of skin or pectoral fascia. 10-yr OS was 54% (+PMRT) and 45% (–PMRT, p < 0.001). Crude cumulative LRR was 32% −PMRT and 9% +PMRT. The survival benefit was seen for all pts (N0-N3).

What are some criticisms of Premenopausal Danish Trial DBCG 82b?

Criticisms of Premenopausal Danish Trial 82b include the inadequate surgical Tx of axilla resulting in a median of 7 nodes removed (which is low), an excess of LF occurring in the axilla (44% in the CMF arm was concerning), and the use of outdated CMF chemo.

What were the design and trial outcomes of Postmenopausal Danish Trial 82c?

In Postmenopausal Danish Trial 82c, 1,375 postmenopausal women <70 yo were randomized to postmastectomy tamoxifen × 1 yr vs. tamoxifen + PMRT. Inclusion criteria, surgical characteristics, and RT were as for Premenopausal Danish Trial 82b. PMRT significantly improved LR (−PMRT 35% vs. +PMRT 8%), DFS (−PMRT 24% vs. +PMRT 36%), and OS (−PMRT 34% vs. +PMRT 45%) at 10-yrs follow-up (all significant).

What are some criticisms of Postmenopausal Danish Trial 82c?

In Postmenopausal Danish Trial 82c, as in Premenopausal Danish Trial 82b, inadequate surgical Tx of the axilla resulted in a median of only 7 axillary LNs removed at surgery. A suboptimal duration of tamoxifen was also employed (1 yr vs. the typical 5 yrs).

What was the surgery in the Danish 82b and 82c trials?

Pts were surgically managed with total mastectomy + axillary LN sampling (aimed at removing at least 5 LNs, full dissection was not required). A median of 7 nodes were removed. 15% had only 0–3 LNs removed, and 75% had <9 LNs removed. This is significantly less than most centers in the U.S., where >10 LNs represent adequate dissection.

How was the RT given in the Danish 82b and 82c trials?

For 82b, PMRT was given after cycle 1 of CMF and 3–5 wks postoperatively. For 82c, PMRT was given 2–4 wks postoperatively. The RT dose was 48–50 Gy given in 22–25 fx to the CW with ant photon fields to cover supraclavicular, infraclavicular, and axillary nodes and an ant electron field to cover the IM nodes and CW. Posterior axillary boost (PAB) was used for pts with a large AP diameter.

What was the design of the British Columbia Trial?

In the British Columbia Trial, 318 premenopausal, high-risk pts with positive axillary LNs were randomized to CMF chemo × 6–12 mos vs. CMF + RT. Surgery involved total mastectomy + axillary LND (median removal of 11 LNs). RT used Co-60 to 37.5 Gy in 16 fx. A 5-field technique was employed, including an en face photon field to cover bilat IM nodes.

What are the relevant outcomes of the British Columbia Trial?

In the British Columbia Trial, at 20-yr follow-up, adj RT improved LRR before DM (13% vs. 39%), DFS (48% vs. 31%), and OS (47% vs. 37%) (all significant). The benefit was extended to those with 1–3 LN+ Dz as well as those with >4 LN+ Dz.

What are some criticisms of the British Columbia Trial?

In the British Columbia Trial, LRF was high compared to many current series, CMF chemo was employed, and the RT fields included en face photons for IM nodal coverage (though no excessive cardiac deaths were observed).

What was demonstrated by the most recent EBCTCG RT meta-analysis?

In the most recent EBCTCG meta-analysis (EBCTCG collaborators, Lancet 2005), 78 randomized trials including 42,000 women were included. After BCS, adj RT reduced 5-yr LR from 26% to 7% and increased 15-yr breast cancer mortality from 30.5% to 35.9%. After mastectomy with axillary clearance in node+ pts, PMRT reduced 5-yr LR from 23% to 5% and improved 15-yr breast cancer mortality from 54.7% to 60.1% (both significant); 5.4% in the entire cohort. In pts with node– Dz who had mastectomy with axillary clearance, PMRT reduced 5-yr LR from 6% to 2% (p = 0.0002) but caused a 3.6% increase in the 15-yr breast cancer mortality rate. 5-yr tamoxifen use reduced the LR rate by about one half in pts with ER+ Dz. In all pts, chemo reduced the LR rate by one third. RT was associated with excess contralat breast cancer, lung cancer, and cardiac mortality. Many “older” trials were included in this analysis.

What was demonstrated by the Whelan meta-analysis for PMRT?

The Whelan meta-analysis (Whelan TJ et al., JCO 2000) included 18 relatively recent trials (1967–1999) with 6,367 pts who had mastectomy and chemo. Adj RT was found to be associated with reduced LR (OR 0.25), all recurrence (OR 0.69), and reduced mortality (OR 0.83). The survival benefit was not significant when the Danish trials were excluded.

What was demonstrated by the Gebski meta-analysis for PMRT?

The Gebski meta-analysis (Gebski V et al., JNCI 2006) analyzed 36 unconfounded PMRT trials and stratified these trials according to the appropriate RT dose given (biologic effective dose 40–60 Gy in 2 Gy/fx) and the RT target tissue coverage. Among the 17 series that fit these criteria and had 5-yr follow-up data, adj RT was associated with an absolute 2.9% increase in OS at 5 yrs. Among the 13 series that had 10-yr data, a 10-yr OS benefit of 6.4% was observed.

Have there been any prospective randomized trials evaluating PMRT in pts treated with neoadj chemo?

No. There have been no prospective randomized trials evaluating PMRT in pts treated with neoadj chemo.

What was demonstrated in the retrospective series from MDACC regarding PMRT in pts treated with neoadj chemo?

Huang E. et al. analyzed the outcomes of 542 pts who had been enrolled in prospective clinical trials and treated with neoadj chemo, mastectomy, and RT. These pts were compared to 134 pts enrolled in the same trials who rcv no adj RT. Clinical stage, margin status, and hormone receptor status did not favor the adj RT group. CSS was improved with adj RT in pts with clinical stage IIIB or supraclavicular LN+ Dz, clinical T4 tumors, and pathologically ≥4 +nodes. LRR was improved even for those pts with clinical stage III or supraclavicular LN+ Dz who achieved a pCR on neoadj chemo. (JCO 2004)

What are the present ASCO guidelines for PMRT?

PMRT is recommended for pts with ≥4 +LNs and suggested for T3 tumor with axillary LN Dz or operable stage III Dz.

What is the rationale for not recommending PMRT to pts with <4 positive axillary LNs?

In numerous studies, Dz involvement of 1–3 LNs has been associated with an increased risk of LR compared to those with no LN Dz. Since RT can result in toxicity-related mortality, there is concern that PMRT in this population will lead to worse OS.

What are some arguments for providing PMRT to pts with 1–3 positive axillary LNs?

An argument for treating pts with 1–3 LN Dz with PMRT is that all 3 modern randomized trials (Danish 82b, Danish 82c, and British Columbia) showed significant OS benefit with PMRT. This was true in subgroup analysis of this population and even when analysis was restricted to pts who had at least 8 axillary LNs removed in Danish trials. (Overgaard et al., Radiother Oncol 2007)

In EBCTCG meta-analysis, pts with 1–3 LN Dz had absolute 5-yr LR benefit of 11.6% with PMRT but did not have OS benefit. This was likely b/c their initial LR risk without PMRT was not that high, so PMRT did not generate larger LR benefit. In the same analysis, pts with absolute 5-yr LR benefit of 10%–20% had OS benefit with PMRT. Therefore, PMRT should be considered for pts with 1–3 LN Dz and other high-risk clinicopathologic factors (such as LVSI, ECE >2 mm, +margin, <35–40 yo) that would further increase their LR risk.

What is the argument that the LF rates (and therefore the benefit of PMRT) in pts with N1 Dz (1–3 LN+) seen in the Danish and British Columbia PMRT trials do not necessarily represent the typical experience in this subset of pts in U.S.?

In the ECOG postmastectomy chemo trials (without adj RT) (Fowble B et al., JCO 1988), where the median nodes removed were 12, the 3-yr isolated LRF rate in the 1–3 node pts was 7% but goes up to 15% for 4+ LNs. The cumulative 10-yr LRR +/− DM for pts with 1–3 LN Dz in retrospective review of pts in prospective trials conducted by the NSABP, the ECOG, and MDACC was 4%–13% (Taghian AG et al., JCO 2004; Recht A et al., JCO 1999; Katz A et al., JCO 2000).

For pts who undergo mastectomy with 1–3 +nodes, what other clinicopathologic factors should be considered when recommending PMRT?

Retrospective studies from the IBCSG, NSABP, and MDACC have suggested that factors such as +LVI, high grade, younger age, ECE ≥2 mm, >10 LN examined, ≥20% LN, larger tumor size (T2 or ≥4 cm), and close margins produce 10-yr LRR >15%. So consider PMRT for these pts.

Under what circumstances should regional LN be covered for PMRT (comprehensive PMRT)?

Comprehensive PMRT (CW + LN) is recommended for most pts who have high LRR risk that warrant PMRT since the benefit of RT of regional LN outweighs in most cases the added toxicity. We consider CW RT alone for pts with upfront mastectomy and T3N0 or those with T1-T2N0 who are being treated for +margin only. The results from EORTC 22922/10925 and SUPREMO trials will give us better indication for PMRT use in pts with 1–3 LN involvement.

Should the IM chain be included in all PMRT fields?

This is controversial. Some radiation oncologists believe that since it was covered in the 3 randomized PMRT trials, and a nonrandomized Israeli study (Stemmer SM et al., J Clin Oncol 2003) demonstrated that IM nodal irradiation may improve DFS (73% vs. 52%) and trended to improved OS (78% vs. 64%, p = 0.08), that it should be the gold standard approach. However, others would argue not to include IM nodes routinely since 3 randomized trials examining the role of IM nodal dissection did not improve OS for these pts (Veronesi U et al., Eur J Cancer 1999Meir P et al., Cancer 1989Lacour J et al., Cancer 1976) and that isolated recurrence in the IM is low after whole breast RT without IM node RT, possibly some of the Dz is already included in the tangent field.

A randomized trial (EORTC 22922/10925) testing the effects of IM nodal irradiation on LRC and survival has completed accrual with results pending.

Should pts with T3N0 breast cancer who have had a mastectomy without neoadj chemo be treated with PMRT?

This is controversial. Traditionally, pts with T3N0 without other risk factors have been treated with CW-only PMRT. However, 2 recent retrospective studies have demonstrated that the LF rates are low for T3N0 pts after mastectomy alone with adj chemo, questioning the role of PMRT. This is an evolving area of research, so pts with pT3N0 without other risk factors should be considered for CW-alone PMRT with appropriate discussion of risk and benefits of RT.

Taghian AG et al., JCO 2006: review of an NSABP postmastectomy chemo trial, with 313 pts with ≥5-cm tumors (N0). The 10-yr isolated LRF was 7.1%, and LRF +/− DM was 10%. 24 or 28 LRR was at the CW. However, the median size of the tumor was 5.5 cm, so the data may not be applicable for very large or infiltrative tumors.

Floyd SR et al., IJROBP 2006: review of a multi-institutional database for ≥5-cm tumors (N0). Out of 70 pts, the 5-yr LRF was 7.6%. LVI was a significant prognostic factor for LF.

How is IBC managed?

IBC is managed using combined-modality therapy with neoadj chemo, modified radical mastectomy, and comprehensive PMRT +/− additional chemo (if not completed preoperatively) and hormones (if ER+) and/or Herceptin × 1 yr (if HER2+). Many retrospective studies show 5-yr DFS of 25%–30% and 5-yr OS of ~40%.

What are 2 acceptable PMRT schedules for IBC?

1.     Conventional: 50 Gy comprehensive RT → 66 Gy to CW boost

2.     MDACC: hyperfractionated RT: 1.5 Gy bid to 51 Gy to CW and axilla →15 Gy boost in 10 fx bid to 66 Gy

The LRC from bid RT is promising, with 5- and 10-yr LRC of 84% and 77%, respectively (Liao Z et al., IJROBP 2000).

What are the options for a pt with poor response and unresectable Dz after induction chemo for IBC?

Alternative chemo; if there is still no response, can consider upfront RT (conventional RT or hyperfractionated RT) → consideration for surgery.

For pts who want breast reconstruction after mastectomy, when should the breast reconstruction be done relative to the rest of the adj Tx?

Breast reconstruction should be done 6–12 mos after RT since cosmetic outcome is worse if reconstruction is done before RT. A 2-stage delayed implant is recommended. For saline implants, skin-sparing mastectomy with placement of tissue expanders should be done prior to RT. The tissue expander is deflated during RT and re-expanded afterward.

image Toxicity

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

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

2.     Late: soft tissue fibrosis, breast size change, telangiectasias, lymphedema, pulmonary fibrosis, precocious cardiovascular Dz, 2nd malignancy

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

~20%–30% of pts experience skin breakdown. The most common sites are the inframammary fold and axillary sulcus.

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

After whole breast RT and lumpectomy, ~20%–30% have a less than good or excellent cosmetic result.

What is the rate of lymphedema 5 yrs after whole breast RT +/+ axillary LND? How does the RT technique affect risk?

Lymphedema occurs in ~15%–40% of pts after RT + axillary LND. It occurs in 10%–15% after RT and SLN Bx. The rate of lymphedema with SLN Bx alone is <2%. Retrospective studies suggest that the use of a supraclavicular field to treat the regional nodes increases the risk of lymphedema compared to tangents alone, on the order of 15%–20%. Adding PAB to modified radical mastectomy + axillary and supraclavicular RT increases the rate to 40%–45%.

What is the RR of cardiovascular death after RT?

Studies from the pre-3D planning era suggest that RT for breast cancer is associated with an increase in annual events of cardiovascular death (relative ratio of 1.25, EBCTCG) compared to no RT.

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

From EBCTCG, the relative ratio of annual events compared to no RT is ~1.6–2.