2
risk of radiation therapy–induced CBC for those patients at greater risk. D. E. Wazer, MD Reference 1. Broeks A, Braaf LM, Huseinovic A, et al. Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study. Breast Cancer Res. 2007;9:R26. Ten-year recurrence rates in young women with breast cancer by locoregional treatment approach Beadle BM, Woodward WA, Tucker SL, et al (Univ of Texas M. D. Anderson Cancer Ctr, Houston) Int J Radiat Oncol Biol Phys 73:734-744, 2009 Purpose.—Young women with breast cancer have higher locoregional recurrence (LRR) rates than older patients. The goal of this study is to determine the impact of locoregional treatment strategy, breast-conserving therapy (BCT), mastectomy alone (M), or mastectomy with adjuvant radi- ation (MXRT), on LRR for patients 35 years or younger. Methods and Materials.—Data for 668 breast cancers in 652 young patients with breast cancer were retro- spectively reviewed; 197 patients were treated with BCT, 237 with M, and 234 with MXRT. Results.—Median follow-up for all living patients was 114 months. In the entire cohort, 10-year actuarial LRR rates varied by locoregional treatment: 19.8% for BCT, 24.1% for M, and 15.1% for MXRT (p ¼ 0.05). In patients with Stage II disease, 10-year actuarial LRR rates by locoregional treatment strategy were 17.7% for BCT, 22.8% for M, and 5.7% for MXRT (p ¼ 0.02). On multivariate analysis, M (hazard ratio, 4.45) and Grade III disease (hazard ratio, 2.24) predicted for increased LRR. In patients with Stage I disease, there was no difference in LRR rates based on locoregional treatment (18.0% for BCT, 19.8% for M; p ¼ 0.56), but chemotherapy use had a statistically significant LRR benefit (13.5% for chemotherapy, 27.9% for none; p ¼ 0.04). Conclusions.—Young women have high rates of LRR after breast cancer treatment. For patients with Stage II disease, the best locoregional control rates were achieved with MXRT. For patients with Stage I disease, similar outcomes were achieved with BCT and mastectomy; however, chemo- therapy provided a significant benefit to either approach. Therapeutic decisions for young women with breast cancer are often based on studies where they comprise only a minority of the study population. This analysis by Beadle and colleagues, which evaluated LRR and survival in 652 women age 35 years or less, is an important contribution to the literature focusing on treatment and outcomes in young women with breast cancer. In contrast to other studies comparing BCT to mastectomy regardless of postmastectomy radiation therapy (PMRT) use, the current study specifically compared BCT, mastectomy alone, and mastectomy plus PMRT according to disease stage. This strategy yielded a number of noteworthy findings. 1 In young women with stage I disease, predominantly managed by BCT or mastectomy alone, the 10-year LRR of 18% to 20% was high, but this risk was attenuated by the use of adjuvant chemotherapy. 2 In young women with stage II disease, those treated with PMRT experienced significantly improved locoregional control compared to BCT or mastectomy alone, despite having higher-risk features. 3 In young women with stage III disease, mastectomy alone was associated with higher LRR on multivariate analysis than either BCT or mastectomy plus PMRT, with the latter two having similar outcomes. This study by Beadle and colleagues corroborates other series suggesting that young age alone is not a contraindication to BCT. 1 It affirms that systemic therapy use in young patients with early breast cancer can optimize not only systemic but also locoregional control 2 and reinforces consensus guidelines recommending PMRT for women with advanced tumor stage and extensive nodal burden. 3 Most importantly, this study helps address ongoing debates regarding optimal locoregional treatment for women with stage II breast cancer, including those at intermediate risk with T1-T2 tumors and 0-3 positive nodes. Focusing on stage-specific outcomes with different locoregional treatment strategies, the data in this report are consistent with randomized controlled trials demonstrating that PMRT significantly improves locoregional control in premenopausal patients with node-positive and high-risk Breast Diseases: A Year Book Ò Quarterly 313 Vol 20 No 3 2009

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Page 1: Ten-year recurrence rates in young women with breast cancer by locoregional treatment approach

risk of radiation therapy–inducedCBC for those patients at greater risk.

D. E. Wazer, MD

Reference1. Broeks A, Braaf LM, Huseinovic A,

et al. Identification of women with anincreased risk of developing

Breast Dis

radiation-induced breast cancer:a case only study. Breast Cancer Res.2007;9:R26.

Ten-year recurrence rates inyoung women with breastcancer by locoregionaltreatment approach

Beadle BM, Woodward WA, Tucker SL,et al (Univ of Texas M. D. AndersonCancer Ctr, Houston)

Int J Radiat Oncol Biol Phys 73:734-744, 2009

Purpose.—Young women withbreast cancer have higher locoregionalrecurrence (LRR) rates than olderpatients. The goal of this study is todetermine the impact of locoregionaltreatment strategy, breast-conservingtherapy (BCT), mastectomy alone(M), or mastectomy with adjuvant radi-ation (MXRT), on LRR for patients 35years or younger.

Methods and Materials.—Data for668 breast cancers in 652 youngpatients with breast cancer were retro-spectively reviewed; 197 patientswere treated with BCT, 237 with M,and 234 with MXRT.

Results.—Median follow-up for allliving patients was 114 months. In theentire cohort, 10-year actuarial LRRrates varied by locoregional treatment:19.8% for BCT, 24.1% for M, and15.1% for MXRT (p¼ 0.05). Inpatients with Stage II disease, 10-yearactuarial LRR rates by locoregionaltreatment strategy were 17.7% forBCT, 22.8% for M, and 5.7% forMXRT (p¼ 0.02). On multivariateanalysis, M (hazard ratio, 4.45) andGrade III disease (hazard ratio, 2.24)predicted for increased LRR. In

patients with Stage I disease, therewas no difference in LRR rates basedon locoregional treatment (18.0% forBCT, 19.8% for M; p¼ 0.56), butchemotherapy use had a statisticallysignificant LRR benefit (13.5% forchemotherapy, 27.9% for none;p¼ 0.04).

Conclusions.—Young women havehigh rates of LRR after breast cancertreatment. For patients with Stage IIdisease, the best locoregional controlrates were achieved with MXRT. Forpatients with Stage I disease, similaroutcomes were achieved with BCTand mastectomy; however, chemo-therapy provided a significant benefitto either approach.

Therapeutic decisions for youngwomen with breast cancer are oftenbased on studies where they compriseonly a minority of the studypopulation. This analysis by Beadleand colleagues, which evaluated LRRand survival in 652 women age 35years or less, is an importantcontribution to the literature focusingon treatment and outcomes in youngwomen with breast cancer. In contrastto other studies comparing BCT tomastectomy regardless ofpostmastectomy radiation therapy(PMRT) use, the current studyspecifically compared BCT,mastectomy alone, and mastectomyplus PMRT according to disease stage.This strategy yielded a number ofnoteworthy findings.1 In young womenwith stage I disease, predominantlymanaged by BCT or mastectomy

alone, the 10-year LRR of 18% to 20%was high, but this risk was attenuatedby the use of adjuvant chemotherapy.2

In young women with stage II disease,those treated with PMRT experiencedsignificantly improved locoregionalcontrol compared to BCT ormastectomy alone, despite havinghigher-risk features.3 In young womenwith stage III disease, mastectomyalone was associated with higher LRRon multivariate analysis than eitherBCT or mastectomy plus PMRT, withthe latter two having similaroutcomes.

This study by Beadle andcolleagues corroborates other seriessuggesting that young age alone is nota contraindication to BCT.1 It affirmsthat systemic therapy use in youngpatients with early breast cancer canoptimize not only systemic but alsolocoregional control2 and reinforcesconsensus guidelines recommendingPMRT for women with advancedtumor stage and extensive nodalburden.3 Most importantly, this studyhelps address ongoing debatesregarding optimal locoregionaltreatment for women with stage IIbreast cancer, including those atintermediate risk with T1-T2 tumorsand 0-3 positive nodes. Focusing onstage-specific outcomes with differentlocoregional treatment strategies, thedata in this report are consistent withrandomized controlled trialsdemonstrating that PMRTsignificantly improves locoregionalcontrol in premenopausal patientswith node-positive and high-risk

eases: A Year Book� Quarterly 313Vol 20 No 3 2009

Page 2: Ten-year recurrence rates in young women with breast cancer by locoregional treatment approach

node-negative breast cancer4,5 andsupport the contention that PMRTshould be discussed and offered toyoung patients with stage II disease.

While not reported in this study, itwould be valuable to gain informationon the patterns of local and regionalrecurrence within each treatmentgroup. In particular, the knowledge ofwhere locoregional recurrences occurand how these relate to radiationtreatment volume can help addresscurrently unresolved questionsregarding what constitutes the optimaladjuvant radiation therapy volumeafter breast-conserving surgery andmastectomy. Finally, acknowledgingthat it may be difficult to extrapolatethe results of this study tocontemporary practice in whichsurgical, radiation therapy, andsystemic therapy practices havesignificantly evolved, the findingsgenerated are thought-provoking and

314 Breast Diseases: A Year Book� Quar

Vol 20 No 3 2009

clearly highlight the need for newstrategies to individualizelocoregional treatment selection andimprove outcomes for young womenwith breast cancer.

P. T. Truong, MDT. S. Berrang, MD

References1. Coulombe G, Tyldesley S, Speers C,

et al. Is mastectomy superior tobreast-conserving treatment foryoung women? Int J Radiat OncolBiol Phys. 2007;67:1282-1290.

2. Goldhirsch A, Wood WC, Gelber RD,Coates AS, Thurlimann B, Senn HJ,10th St. Gallen conference. Progressand promise: highlights of theinternational expert consensus on theprimary therapy of early breast cancer2007. Ann Oncol. 2007;18:1133-1144.

terly

3. Recht A, Edge SB, Solin LJ, et al.Postmastectomy radiotherapy:clinical practice guidelines of theAmerican Society of ClinicalOncology. J Clin Oncol. 2001;19:1539-1569.

4. Ragaz J, Olivotto IA, Spinelli JJ, et al.Locoregional radiation therapy inpatients with high-risk breast cancerreceiving adjuvant chemotherapy:20-year results of the BritishColumbia randomized trial. J NatlCancer Inst. 2005;97:116-126.

5. Danish Breast Cancer CooperativeGroup, Nielsen HM, Overgaard M,Grau C, Jensen AR, Overgaard J.Study of failure pattern among high-risk breast cancer patients with orwithout postmastectomy radiotherapyin addition to adjuvant systemictherapy: long-term results from theDanish Breast Cancer CooperativeGroup DBCG 82 b and c randomizedstudies. J Clin Oncol. 2006;24:2268-2275.

Predictors of the risk of fibrosisat 10 years after breastconserving therapy for earlybreast cancer - A study basedon the EORTC trial 22881-10882'boost versus no boost'

Collette S, Collette L, Budiharto T, et al(EORTC Headquarters, Brussels, Belgium;et al)

Eur J Cancer 44:2587-2599, 2008

The EORTC 22881-10882 trial in5178 conservatively treated earlybreast cancer patients showed thata 16 Gy boost dose significantlyimproved local control, but increasedthe risk of breast fibrosis. To investi-gate predictors for the long-term riskof fibrosis, Cox regression models ofthe time to moderate or severe fibrosis

were developed on a random set of1797 patients with and 1827 patientswithout a boost, and validated in theremaining set. The median follow-upwas 10.7 years. The risk of fibrosissignificantly increased (P < 0.01) withincreasing maximum whole breast irra-diation (WBI) dose and with concomi-tant chemotherapy, but wasindependent of age. In the boost arm,the risk further increased (P < 0.01) ifpatients had post-operative breastoedema or haematoma, but it decreased(P < 0.01) if WBI was given with>6 MV photons. The c-index wasaround 0.62. Nomograms with thesefactors are proposed to forecast thelong-term risk of moderate or severefibrosis.

We would like to applaud Colletteand colleagues for doing an excellent

job in developing and internally andexternally validating the firstnomogram for predicting the risk offibrosis in women who undergo breast-conserving therapy for early-stagebreast cancer. Currently, clinicians donot have a reliable way of predictingthe risk of fibrosis as they attempt tomaximize local control with a tumorbed boost dose of radiation afterwhole-breast radiation therapy whileminimizing negative cosmeticoutcome. The EORTC ‘‘boost versusno boost’’ trial clearly demonstratedthat while the boost decreased thelocal recurrence risk, the risk of breastfibrosis was significantly higher in theboost group at 10 years than in the noboost group.1 This nomogramprovides physicians with a tool to helpthem navigate the decision-makingprocess regarding boost radiation