Is Mastectomy Superior to Breast-Conserving Treatment for Young Women?

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Int. J. Radiation Oncology Biol. Phys., Vol. 67, No. 5, pp. 1282–1290, 2007Copyright © 2007 Elsevier Inc.

Printed in the USA. All rights reserved0360-3016/07/$–see front matter

doi:10.1016/j.ijrobp.2006.11.032

LINICAL INVESTIGATION Breast

IS MASTECTOMY SUPERIOR TO BREAST-CONSERVING TREATMENT FORYOUNG WOMEN?

GENEVIÈVE COULOMBE, M.D., * SCOTT TYLDESLEY, M.D.,*†� CAROLINE SPEERS, B.A.,†

CHUCK PALTIEL, M.SC.,‡ CHRISTINA AQUINO-PARSONS, M.D.,*� VANESSA BERNSTEIN, M.D.,§�

PAULINE T. TRUONG, M.D.,†¶� MIRA KEYES, M.D.,*�AND IVO A. OLIVOTTO, M.D.†¶�

*From the Radiation Therapy Program, †Breast Cancer Outcomes Unit, and ‡Population and Preventive Oncology Program, BritishColumbia Cancer Agency (BCCA), Vancouver, BC, Canada; §Systemic Therapy Program and ¶Radiation Therapy Program, BCCA,

Vancouver Island Centre, Victoria, BC, Canada; and �University of British Columbia, Vancouver, BC, Canada

Purpose: To examine whether modified radical mastectomy (MRM) improves outcomes compared with breast-conserving treatment (BCT) in young women.Methods and Materials: Women aged 20–49 years, diagnosed with early breast cancer between 1989 and 1998,were identified. Management with BCT or MRM was compared for local (L), locoregional (LR), and distantrelapse-free survival (DRFS) and breast cancer–specific survival (BCSS) by age group (20–39 years, 40–49years). The analysis was repeated for patients considered “ideal” candidates for BCT: tumor size <2 cm,pathologically negative axillary nodes, negative margins, and no reported ductal carcinoma in situ.Results: A total of 1,597 women received BCT, and 801 had MRM. After a median follow-up of 9.0 years, theoutcomes (L, LR, BCSS) were worse for the younger age group; however, the outcomes were not statisticallydifferent by type of local treatment. For women aged 20–39 years considered “ideal” for BCT, those treated withBCT had slightly lower LRFS compared with those treated with MRM (p � 0.3), but DRFS and BCSS weresimilar.Conclusions: A difference in LRFS at 10 years potentially favored MRM among women aged 20–39 yearsconsidered “ideal” BCT candidates but was not statistically significant and did not translate into a noticeabledifference in DRFS or BCSS. Our data suggest that young age alone is not a contraindication to BCT.© 2007 Elsevier Inc.

Breast cancer, Young age, Mastectomy, Breast-conserving treatment, Radiation therapy.

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INTRODUCTION

oung women with early breast cancer have worse out-omes than older women (1–8). Younger women have aigher risk of local and locoregional recurrences than olderomen, and a worse survival. In a study from The Nether-

ands, patients younger than 45 years had a relative risk ofeveloping local recurrence of 4.09 compared with patientsged �65 years (2). A pooled analysis of two randomizedrials comparing breast-conserving treatment (BCT) withodified radical mastectomy (MRM) demonstrated a higher

isk of locoregional relapse and a trend to an increased riskf distant relapse in young women (�35 years); thesencreased risks were not seen in the other age groups (2). Ineneral, local relapse has been associated with an increasedisk of distant metastasis and death (1, 2). However, itemains unclear whether local recurrences were causing

Reprint requests to: Scott Tyldesley, BC Cancer Agency, Van-ouver Centre, 600 West 10th Ave., Vancouver, BC V5Z 4E6,anada. Tel: (604) 877-6000, ext. 2665; Fax: (604) 877-0505;-mail: [email protected]
Presented in part at the Canadian Association of Radiation A
1282

ubsequent dissemination or were a marker of more aggres-ive disease from the outset.

Young age and an extensive intraductal component areignificantly associated with an increased risk of local recur-ence (8). Young age and microscopic involvement of thexcision margin are independent predictors for distant diseasefter BCT (4). Vascular invasion is predictive of local recur-ence, and tumor size, nodal status, high histologic grade, andascular invasion are significant predictors of distant disease,ndependent of the type of surgery (5, 7). A recursive parti-ioning analysis of 900 patients from the Fox Chase Cancerenter (8) suggested that patients aged �35 years were not atigher risk of local recurrence when treated by BCT, if exten-ive intraductal component was absent and if margin proximity�2 mm) was taken into account. It is therefore uncertainhether young age alone is sufficient to deny BCT or whetherCT should only be offered to selected younger patients.

ncologists’ Annual Scientific Meeting, September 8–11, 2005,ictoria, BC, Canada.Conflict of interest: none.Received Oct 10, 2006 and in revised form Nov 10, 2006.

ccepted for publication Nov 16, 2006.

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1283Breast conservation in young women ● G. COULOMBE et al.

This is a report of a population-based evaluation of 10-ear local, regional, and distant recurrence and survivalutcomes in a large cohort of young women with early-tage breast cancer treated with either BCT or mastectomy.n light of the findings from the aforementioned Europeanandomized trials, our hypothesis was that MRM wouldesult in improved outcomes for patients aged 20–39 years,hen compared with BCT at a population level. In patients

t very high risk of systemic relapse it is less likely that theype of local therapy would ultimately impact on breastancer–specific survival (BCSS), and therefore we furtherypothesized that the subgroup for whom the type of localreatment may be most relevant to survival would be aow-risk subgroup ideal for BCT. Therefore, comparisonetween MRM and BCT was also done within a selectroup of patients with a lower risk of local or distantecurrence considered to be “ideal” for BCT. To determinehether any differences in outcome were unique to theounger age group, we repeated the analysis in a group aged0–49 years, controlling for tumor and treatment charac-eristics. The primary outcome for our analysis was BCSS.he secondary outcomes were local, locoregional, and dis-

ant recurrence as first events.

METHODS AND MATERIALS

election and description of participantsBritish Columbia (BC) has a population of just over 4 million

nd has a universal access public health care system. The BCancer Agency (BCCA) has the mandate to provide a provincialancer control program including prevention, screening, diagnosis,nd treatment services. The BCCA manages the budget for allntineoplastic drugs and provides 100% of the radiotherapy (RT)elivered in BC. Within the BCCA’s research mandate, the Breastancer Outcomes Unit (BCOU) has been developed. The BCOUaintains a prospectively assembled database that includes demo-

raphic, stage, pathology, treatment, and outcome information onll breast cancer patients diagnosed since 1989 who were referredo a BCCA center. The BCOU data were retrospectively analyzedor the patient demographics and outcomes of interest.

Women aged 20–49 years, diagnosed between January 1, 1989nd December 31, 1998 who were referred to the BCCA witharly-stage breast cancer (pT1/T2, pN0/N1/NX, �3 positive axil-ary lymph nodes, M0) (9) were included. Patients with locallydvanced or metastatic disease (clinical or pathologic T3, T4, N2,3, or M1 disease), those who had neoadjuvant chemotherapy orT, patients with primary breast sarcomas or lymphomas, patientsith prior invasive or in situ breast or other cancers (except treated

utaneous basal or squamous cell carcinoma, or carcinoma in situf the cervix) were excluded. The study had University of Britisholumbia-BCCA research ethics board approval (R04-0147).Patients who received BCT and those with MRM with or

ithout RT to the chest wall were analyzed. Patients receiving RTo the chest wall after MRM were included because it was recog-ized that the occasional use of chest wall RT in this setting wouldainly be for patients with positive margins after MRM, and

xcluding such cases would potentially bias against BCT. Breast-onserving surgery (BCS) was defined as any open surgery on the
reast less than total mastectomy. The decision to use BCT was c
enerally made before referral to the BCCA. Women having hadCS without radiation to the breast were excluded. Patients who

eceived nodal RT, whether after BCT or MRM, were also ex-luded, because it was recognized that the effect of nodal RT onhe regional relapse rate may bias the results if there was aignificant imbalance in the use of nodal RT in the BCT group.

A previous BCOU study identified that breast cancer patientsged �40 years had a worse prognosis compared with olderatients (5). Therefore, age �40 years was used to define “youngge.”

Patients with tumor size �2 cm, pathologically negative axillaryymph nodes, clear surgical margins, and no extensive ductalarcinoma in situ (DCIS) on the original pathology report wereonsidered “ideal” candidates for BCT and were analyzed as andditional subgroup. It should be noted that the BCOU includesoth centrally reviewed and non–centrally reviewed pathologyeports, and the definition of extensive DCIS did not have atandardized definition.

atient tumor and treatment information abstractedThe following patient and tumor factors were abstracted from

he BCOU database: age, laterality, location (central, medial, lat-ral, multifocal, or unspecified), tumor size, histology (ductalincluding tubular and colloid], lobular [including mixed types],nd other [including medullary]), histologic grade (I, II, III, un-nown), margins (unknown, positive, or negative), lymphovascu-ar invasion (present, absent, unknown), reported DCIS (present,bsent), estrogen receptor status (positive, negative, unknown),nd the number of positive axillary lymph nodes at surgical dis-ection. The following treatment factors were abstracted: type ofreast surgery (mastectomy, BCS), type of axillary surgery (none,issection) (note that this was in an era predating the use ofentinel node dissections), and the number of lymph nodes re-oved. The radiation volume (none, breast/chest wall, nodes,

reast/chest wall plus nodes), the dose and fractionation of radia-ion, and the type of adjuvant systemic therapy (none, hormonalherapy, chemotherapy, or both) were also abstracted.

tatistical analysisAll endpoints were calculated as the interval from the pathologic

iagnosis of breast cancer to the event. Local recurrence was aecurrence in the ipsilateral breast, overlying skin, or chest wall.ocoregional recurrence was the first ipsilateral local or regionalodal recurrence. For both endpoints, patients were censored at thearliest of the following dates: distant relapse occurring �30 daysefore the local/locoregional relapse, subsequent contralateralreast cancer occurring before the local/locoregional relapse, datef death, or last follow-up. When a local and/or regional relapseccurred within 30 days of a distant relapse, the relapses wereonsidered concurrent and were recorded as occurring on the datef the earlier of the events. Distant relapse-free survival (DRFS)as the time from diagnosis to the first relapse beyond the ipsi-

ateral breast and regional lymph nodes. In the calculation ofRFS, the patient was censored at the time of a subsequent

ontralateral new primary breast cancer occurring before a distantelapse, date of death, or last follow-up. Breast cancer–specificurvival was calculated as the time between initial diagnosis andeath when breast cancer was the primary or underlying cause ofeath.Groups were compared using t tests for continuous patient

haracteristics, and Pearson chi-square tests for categorical patient

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1284 I. J. Radiation Oncology ● Biology ● Physics Volume 67, Number 5, 2007

Table 1. Patient and tumor characteristics for all patients

BCT age 20–39 y MRM age 20–39 y p* BCT age 40–49 y MRM age 40–49 y p*

otal 356 184 1,241 617ge at diagnosis (y)20–24 4 (1.1) 1 (0.5) 0.91625–29 23 (6.5) 13 (7.1)30–34 94 (26.4) 49 (26.6)35–39 235 (66.0) 121 (65.8)40–44 544 (43.8) 266 (43.1) 0.76745–49 697 (56.2) 351 (56.9)

ize of lesion (cm)0.01– 0.5 8 (2.2) 15 (8.2) �0.001 54 (4.4) 51 (8.3) �0.0010.6–1.0 46 (12.9) 17 (9.2) 219 (17.6) 78 (12.6)1.1–2.0 184 (51.7) 66 (35.9) 628 (50.6) 208 (33.7)2.1–3.0 92 (25.8) 41 (22.3) 253 (20.4) 166 (26.9)3.1–4.0 22 (6.2) 34 (18.5) 65 (5.2) 83 (13.5)4.1–5.0 4 (1.1) 11 (6.0) 19 (1.5) 27 (4.4)Unknown 0 0 3 (0.2) 4 (0.6)

o. of positive nodes0 270 (75.8) 120 (65.2) 0.018 975 (78.6) 418 (67.7) �0.0011–3 84 (23.6) 60 (32.6) 249 (20.1) 187 (30.3)Unknown 2 (0.6) 4 (2.2) 17 (1.4) 12 (1.9)

o. of nodes recovered1–5 34 (9.6) 16 (8.7) 0.369 129 (10.4) 75 (12.2) 0.2156–10 140 (39.3) 59 (32.1) 453 (36.5) 195 (31.6)11–15 105 (29.5) 65 (35.3) 382 (30.8) 196 (31.8)�15 75 (21.1) 40 (21.7) 249 (20.1) 132 (21.4)Unknown 2 (0.6) 4 (2.2) 28 (2.3) 19 (3.1)

R status at diagnosisNegative 134 (37.6) 4 (34.8) 0.199 343 (27.6) 172 (27.9)Positive 172 (48.3) 02 (55.4) 728 (58.7) 349 (56.6) 0.517Unknown 50 (14.0) 8 (9.8) 170 (13.7) 96 (15.6)

rade at diagnosis1 22 (6.2) 6 (3.3) 0.377 145 (11.7) 59 (9.6) 0.4592 115 (32.3) 59 (32.1) 562 (45.3) 278 (45.1)3 210 (59.0) 110 (59.8) 500 (40.3) 251 (40.7)Unknown 9 (2.5) 9 (4.9) 34 (2.7) 29 (4.7)

V invasion at diagnosisAbsent 209 (58.7) 111 (60.3) 0.411 870 (70.1) 384 (62.2) 0.005Present 141 (39.6) 64 (34.8) 346 (27.9) 206 (33.4)Unknown 6 (1.7) 9 (4.9) 25 (2.0) 27 (4.4)argin statusNegative/close 300 (84.3) 156 (84.8) 0.352 1043 (84.0) 551 (89.3) 0.002Positive 32 (9.0) 12 (6.5) 116 (9.3) 33 (5.3)Unknown/missing 24 (6.7) 16 (8.7) 82 (6.6) 33 (5.3)

umor locationCentral 7 (2.0) 15 (8.2) �0.001 55 (4.4) 64 (10.4) �0.001Medial 80 (22.5) 39 (21.2) 306 (24.7) 99 (16.0)Lateral 208 (58.4) 78 (42.4) 701 (56.5) 298 (48.3)Multifocal 4 (1.1) 20 (10.9) 17 (1.4) 77 (12.5)Unspecified 57 (16.0) 32 (17.4) 162 (13.1) 79 (12.8)

rimary histologyDuctal 337 (94.7) 177 (96.2) 0.682 1151 (92.7) 562 (91.1) 0.005Lobular 4 (1.1) 2 (1.1) 63 (5.1) 50 (8.1)Other 15 (4.2) 5 (2.7) 27 (2.2) 5 (0.8)

oticeable DCISNo 321 (90.2) 149 (81.0) 0.003 1047 (84.4) 465 (75.4) �0.001Yes 35 (9.8) 35 (19.0) 194 (15.6) 152 (24.6)

ateralityLeft 179 (50.3) 91 (49.5) 0.856 591 (47.6) 314 (50.9) 0.184Right 177 (49.7) 93 (50.5) 650 (52.4) 303 (49.1)

nitial hormonal therapyYes 44 (12.4) 19 (10.3) 0.485 198 (16.0) 129 (20.9) 0.008No 312 (87.6) 165 (89.7) 1043 (84.0) 488 (79.1)

(Continued)

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haracteristics. Survival data were analyzed and curves for localL)RFS, locoregional (LR)RFS, DRFS, and BCSS were generatedsing the Kaplan-Meier method, with comparisons made using theog–rank test. Proportionality of hazards was not met for allariables. Therefore, a forward binary logistic regression, ratherhan a Cox regression, was used for the multivariable analysis.ogistic regression was performed on patients without missingata for the included variables and with a minimum of 10 years’ollow-up for the 10-year analysis. Statistical tests were two-tailednd were performed using SPSS 13.0 (SPSS, Chicago, IL).

The covariates in the multivariable analysis were age, size ofesion, tumor location, number of positives nodes, estrogen recep-or (ER) status, grade, lymphovascular status, margin status, pri-ary histology (ductal, lobular, other), presence or absence of

oticeable DCIS, and the use or not of initial adjuvant hormonalherapy or chemotherapy. These variables were entered into thenalysis using a stepwise procedure. Once the best model waselected, local surgery was entered into the logistic regression last,o isolate its impact as much as possible. Because the use of RTas highly related to the type of surgery, RT data were not

ncluded in the analysis as a separate variable.

RESULTS

In total, 3,067 patients met the basic inclusion criteria. Ofhose, 669 were excluded because of nodal radiation (n �70) or BCS without radiation of the breast (n � 99).herefore 2,398 patients were included in the study group:,597 had BCS plus RT to the breast and 801 had mastec-omy with (n � 64) or without (n � 737) RT to the chestall. The median follow-up time was 9.0 years.There were several imbalances in the tumor characteris-

ics between the BCT and MRM groups. The MRM groupenerally had worse prognostic factors (Tables 1 and 2), inarticular slightly larger tumors and more nodal involve-ent.Compared with patients receiving BCT, patients treated

ith MRM had larger tumors. In the group aged 20–39ears, the mean size was 1.89 cm for BCT, compared with

Table 1. Patient and tumor char

BCT age 20–39 y MRM age 20–3

nitial chemotherapyYes 243 (68.3) 135 (73.4)No 113 (31.7) 49 (26.6)

xillary node dissectionYes 353 (99.2) 182 (98.9)No 3 (0.8) 2 (1.1)

nitial RTNone 0 165 (89.7)Br/Ch wall alone 240 (67.4) 18 (9.8)Br/Ch wall � boost 116 (32.6) 1 (0.5)

Abbreviations: BCT � breast-conserving treatment; MRM � Mascular; DCIS � ductal carcinoma in situ; RT � radiotherapy; BNumbers in parentheses are percentages. Hormonal therapy statu

ormonal therapy. Chemotherapy status: 1 patient aged �40 y wa* Unknowns excluded; chi-square test.

.25 cm for MRM (p � 0.001), and in the older group, aged 0

0–49 years, the means were 1.75 cm and 2.09 cm, respec-ively (p � 0.001). The tumor was more frequently centralr multifocal, associated with more involved nodes or no-iceable DCIS for the patients who chose to receive mas-ectomy. Patients having BCT were more likely to haveositive margins. Lymphovascular invasion was slightlyore frequent for the younger cohort, and for the women

ged 40–49 years it was more often detected among thosereated with MRM. There were no difference in the ERtatus of the BCT and MRM groups for the younger pa-ients, but there were more ER-positive tumors in the olderatients treated by BCT.Among the “ideal” breast conservation patients, the mean

umor size was similar in the two age groups comparing theCT and MRM groups. Even when restricted to patientsideal” for BCT, there were still more central or multifocalumors treated by MRM.

In addition, the groups were not balanced for adjuvantherapy use. Hormonal therapy and chemotherapy use wereimilar for the younger patients receiving BCT or MRM, butor the older patients, adjuvant systemic therapy was usedore commonly if patients had received MRM. All of the

atients treated with BCS had RT to the breast. In compar-son, 10.3% and 7.3% of the patients treated with mastec-omy had adjuvant RT if aged 20–39 years or 40–49 years,espectively. The median radiation dose was 44 Gy in 16aily fractions to the breast and 40 Gy in 16 daily fractionso the chest wall, 5 days per week.

For all outcomes, the younger patients did worse. The0-year rates of LRFS, LRRFS, DRFS, and BCSS were5.3% vs. 92.3%, 82.0% vs. 88.7%, 72.9% vs. 84.1%, and8.1% vs. 87.3% (all p � 0.001) for patients aged 20–39ears vs. patients aged 40–49 years, respectively.Comparing BCT with MRM for patients aged 40–49

ears, LRFS (95.2% vs. 91.8%, p � 0.34) and LRRFS89.2% vs. 87.6%, p � 0.16) were similar at 10 years, buthe differences between DRFS (86.4% vs. 79.6%, p �

tics for all patients (Continued)

p* BCT age 40–49 y MRM age 40–49 y p*

0.219 618 (49.8) 365 (59.2) �0.001623 (50.2) 252 (40.8)

0.779 1224 (98.6) 610 (98.9) 0.67217 (1.4) 7 (1.1)

�0.001 0 572 (92.7) �0.001864 (69.6) 36 (5.8)377 (30.4) 9 (1.5)

d-radical mastectomy; ER � estrogen receptors; LV � lympho-reast; Ch � chest.tient aged �40 y was unknown and assumed not to have receivedown and assumed not to have received chemotherapy.

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.001) and BCSS (89.0% vs. 83.9%, p � 0.002) were

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ignificantly different in favor of BCT, reflecting the imbal-nce of prognostic factors. For subjects aged 20–39 years,ifferences in outcomes at 10 years disappeared (LRFS 86%s. 83.8%, p � 0.34; LRRFS 82.6% vs. 80.9%, p � 0.41;RFS 73.1% vs. 72.5%, p � 0.77; BCSS 79.8% vs. 74.9%,� 0.09) for BCT vs. MRM, respectively.

Table 2. “Ideal” BCT group

BCT age 20–39 y MRM age 2

otal 131 43ge at diagnosis (y)20–24 2 (1.5) 025–29 12 (9.2) 4 (9.3)30–34 29 (22.1) 10 (23.335–39 88 (67.2) 29 (67.440–4445–49

ize of lesion (known) (cm)0.1–0.5 4 (3.1) 6 (14.00.6–1.0 26 (19.8) 8 (18.61.1–2.0 101 (77.1) 29 (67.4

o. of nodes recovered1–5 12 (9.2) 4 (9.3)6–10 57 (43.5) 17 (39.511–15 36 (27.5) 16 (37.2�15 26 (19.8) 6 (14.0Unknown 0 0

R status at diagnosisNegative 47 (35.9) 15 (34.9Positive 62 (47.3) 24 (55.8Unknown 22 (16.8) 4 (9.3)

rade at diagnosis1 13 (9.9) 4 (9.3)2 45 (34.4) 14 (32.63 72 (55.0) 24 (55.8Unknown 1 (0.8) 1 (2.3)

V invasion at diagnosisAbsent 94 (71.8) 30 (69.8Present 35 (26.7) 11 (25.6Unknown/not applicable 2 (1.5) 2 (4.7)

umor locationCentral 2 (1.5) 4 (9.3)Medial 32 (24.4) 7 (16.3Lateral 74 (56.5) 15 (34.9Multifocal 2 (1.5) 8 (18.6Unspecified 21 (16.0) 9 (20.9Primary histologyDuctal 128 (97.7) 43 (100Lobular 1 (0.8) 0Other 2 (1.5) 0

nitial hormonal therapyYes 7 (5.3) 2 (4.7)No 124 (94.7) 41 (95.3

nitial chemotherapyYes 59 (45.0) 23 (53.5No 72 (55.0) 20 (46.5

nitial RTNone 0 41 (95.3Br/Ch wall alone 97 (74.0) 2 (4.7)Br/Ch wall � boost 34 (26.0) 0

Abbreviations as in Table 1. Ideal � negative margins, tumor* Unknowns excluded; chi-square test.

For the subset of patients aged 40–49 years considered m

ideal” for BCT, there were no differences in any 10-yearutcomes by type of surgery (LRFS 92.6% vs. 93.1%, p �.99; LRRFS 91.8% vs. 91.2%, p � 0.75; DRFS 92.7% vs.7.6%, p � 0.16; BCSS 93.8% vs. 93.3% p � 0.80). For theounger patients considered “ideal” for BCT there was aonsignificant difference favoring LRFS at 10 years in the

t and tumor characteristics

p* BCT age 40–49 y MRM age 40–49 y p*

507 157

0.879 0.217

222 (43.8) 60 (38.2)285 (56.2) 97 (61.8)

0.0282 24 (4.7) 18 (11.5) 0.010129 (25.4) 35 (22.3)354 (69.8) 104 (66.2)

0.624 61 (12.0) 21 (13.4) 0.138195 (38.5) 44 (28.0)152 (30.0) 56 (35.7)93 (18.3) 33 (21.0)6 (1.2) 3 (1.9)

0.428 116 (22.9) 29 (18.5) 0.030311 (61.3) 89 (56.7)80 (15.8) 39 (24.8)

0.980 78 (15.4) 22 (14.0) 0.752263 (51.9) 86 (54.8)151 (29.8) 43 (27.4)15 (3.0) 6 (3.8)

0.970 422 (83.2) 124 (79.0) 0.76879 (15.6) 25 (15.9)

6 (1.2) 8 (5.1)

�0.001 25 (4.9) 16 (10.2) �0.001126 (24.9) 22 (14.0)285 (56.2) 71 (45.2)

3 (0.6) 28 (17.8)68 (13.4) 20 (12.7)

0.606 472 (93.1) 145 (92.4) 0.05223 (4.5) 12 (7.6)12 (2.4) 0

0.859 47 (9.3) 19 (12.1) 0.300460 (90.7) 138 (87.9)

0.335 134 (26.4) 47 (29.9) 0.389373 (73.6) 110 (70.1)

�0.001 0 148 (94.3) �0.001389 (76.7) 9 (5.7)118 (23.3) 0

, pN0, no extensive DCIS.

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ocal control curves diverged after 8 years, but at 10 yearshere was no obvious impact on the other outcomes com-aring BCT with MRM (LRRFS 84.0% vs. 87.3%, p �.94; DRFS 85.7% vs. 75.4%, p � 0.17; BCSS 90.8% vs.6.0%, p � 0.41) (Figs. 1 and 2).

The multivariable model for each outcome was builtsing a likelihood ratio–based, forward stepwise methodTable 3).

For the whole group with follow-up at 10 years (951atients), young age was associated with worse prognosisor all outcomes. The odds ratios for an event were 1.6–2.2or women age 20–39 years compared with women aged0–49 years. Positive margins were associated with moreocal and locoregional recurrences. Lymph node positivityas associated with an increased local relapse rate. Lym-hovascular invasion was associated with more locore-ional and distant relapses. Larger tumor size and positive

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Fig. 1. Kaplan-Meier curves for local relapse-free sursurvival, and breast cancer specific survival for the “ideawith radiotherapy; MRM � modified radical mastectom

ymph node status were associated with a higher rate of r

istant relapse and lower BCCS. Grade 3 histology wasssociated with lower BCSS. For the whole group, patientsreated with MRM had significantly worse LRRFS thanatients treated with BCS (relative risk � 1.6, p � 0.025).

DISCUSSION

Local recurrence can be a sign of a more aggressiveumor and/or a source for metastatic dissemination. If it is aource of dissemination, better local control should improveRFS and BCSS outcomes. Patients treated with BCS with-ut RT have significantly higher rates of local recurrencend also have worse BCSS compared with patients treatedith BCS plus RT (10, 11).Randomized controlled trials have demonstrated that

CS followed by RT provides local control and survivalenerally equivalent to that seen with MRM (12, 13). In

1086420

Time to locoregional relapse (years)

1.0

0.8

0.6

0.4

0.2

0.0

BCT

MRM

p = 0.94

1086420

Time to breast cancer death (years)

1.0

0.8

0.6

0.4

0.2

0.0

BCT

MRM

p = 0.41

locoregional relapse-free survival, distant relapse-freep, aged 20–39 years. BCT � breast-conserving therapy

Loco

regi

onal

rela

pse-

free

sur

viva

lB

reas

t can

cer-

spec

ific

surv

ival

vival,l” grou

etrospective series and randomized trials, young women

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ave higher local recurrence rates after BCT compared withlder women (4, 5). Relatively few very young patientsere included in the randomized trials of BCT comparedith mastectomy, and it therefore remains unclear whether

he survival of very young patients might be compromisedy higher local recurrence rates if treated with BCT insteadf MRM.The pooled data of Voogd et al. (4) from two randomized

uropean studies, EORTC 10801 and DBCG-82TM, sug-ested that the absolute increase in the local relapse rate was8% higher (statistically significant) and the distant relapseate was 8% higher (not statistically significant) at 10 yearsn women aged �35 years treated with BCT compared withastectomy. Whether the absence of statistical significance

or DRFS reflects an inadequate power or the absence of a

1086420

Time to local relapse (years)

1.0

0.8

0.6

0.4

0.2

0.0

Loca

l rel

apse

-free

sur

viva

l

BCT

MRM

p = 0.99

1086420

Time to distant relapse (years)

1.0

0.8

0.6

0.4

0.2

0.0

Dis

tant

rela

pse-

free

sur

viva

l

BCT

MRM

p = 0.16

(a)

(b)

Fig. 2. Kaplan-Meier curves for local relapse-free sursurvival, and breast cancer specific survival for the “ideawith radiotherapy; MRM � modified radical mastectom

eal difference in outcome is unclear. Conversely, a large t

rospective (but not randomized) database including morehan 700 patients aged �35 years at diagnosis and 2,200atients aged �40 years at diagnosis suggested that overallurvival was not compromised with BCT relative to mas-ectomy in young patients (14).

It must be acknowledged that retrospective studies areore difficult to analyze because of the possibility of im-

alanced prognostic factors and bias in treatment selection.urthermore, risk factors such as margin status after MRMr BCT may have different implications, and thereforeccounting for them in a multivariate analysis is problem-tic. It is possible that such biases prohibit our ability todentify a true difference between BCT and MRM in theseatients. However, retrospective studies also reflect the re-lity of daily practice and contribute useful insights about

1086420

Time to locoregional relapse (years)

1.0

0.8

0.6

0.4

0.2

0.0

Loco

regi

onal

rela

pse-

free

sur

viva

l

BCT

MRM

p = 0.75

1086420

Time to breast cancer death (years)

1.0

0.8

0.6

0.4

0.2

0.0

Bre

ast c

ance

r-sp

ecifi

c su

rviv

al

BCT

MRM

p = 0.80

locoregional relapse-free survival, distant relapse-freep, aged 40–49 years. BCT � breast-conserving therapy

vival,l” grou

he outcome of the care provided.

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The present population-based, retrospective study con-rmed that at 10 years, women aged 20–39 years at diag-osis had inferior outcomes compared with women aged0–49 years. This worse prognosis has been observed bythers (1–8). In our general study population, we observedhat patients treated with MRM did worse than patients whoad BCT, as a result of an imbalance of prognostic factorsetween the treatment groups.For the multivariable analysis at 10 years, all patients

ere analyzed together. In that analysis, young age wasssociated with inferior RFS and BCSS, supporting theoncern that young age at diagnosis of breast cancer isssociated with a worse prognosis. Extensive DCIS wasot found to be significant, but this could be related to theossibility of being under-reported in the database, asell as having a lesser effect in patients treated withastectomy.The subset of patients identified as being “ideal” for BCT

ad negative margins, no reported extensive DCIS, tumorize �2 cm, and pathologically negative axillary lymphodes. When restricting the analysis to the “ideal” patients,ge 20–39 years was still associated with inferior RFS andCSS compared with the older cohort. The analysis by typef surgery at 10 years suggested a potential improvement in

Table 3. Multivariable analysis at 10 years

Local RFS Locoregional RFS

Margin� Margin�(OR 2.3, p � 0.012) (OR 2.02, p � 0.024Young age LV�(OR 2.16, p � 0.003) (OR 1.94, p � 0.002LN� Young age(OR 1.67, p � 0.046) (OR 1.8 , p � 0.0014

Mastectomy(OR 1.6, p � 0.025

Abbreviations: RFS � relapse-free survival;ratio; LV � lymphovascular; LN� � lymph

ocal control for the “ideal” young women treated with c

REFEREN

RM, but this was not statistically significant and did notranslate into improved distant control or better BCSS.lthough this potential difference is clearly not statistically

ignificant, the comparison is limited by the small sampleize, which limits our ability to make a definitive conclu-ion.

Among the older patients considered ideal candidates forCT, the outcomes were very similar whether treated withRM or BCT, supporting the idea that the nonsignificant

ifference seen in the younger patients may be real. Statis-ical significance may not have been reached owing to themall number of young patients. Moreover, although themproved local control in “ideal” young women treated with

RM might be due to random variation, previous studies15) support the hypothesis that more aggressive treatmentmproves local control.

Women aged 20 –39 years at diagnosis had higher ratesf local, locoregional, and distant recurrence and deathrom breast cancer compared with women aged 40 – 49ears. The 10-year LRFS and LRRFS among womenged 20 –39 years considered ideal for BCT favored theastectomy group, but the differences were not statisti-

ally significant and did not translate into worse DRFS orCSS. These data suggest that young age alone is not a

l cases with complete follow-up available

Distant RFS BCSS

Size �3.0 cm Size �3.0cmOR 5.93, p � 0.016) (OR 7.6, p � 0.049)

LV� Grade 3R 2.14, p � 0.001) (OR 3.8, p � 0.03)

LN� LN�OR 1.74, p � 0.002) (OR 1.97, p � 0.001

Young age LV�OR 1.64, p � 0.005) (OR 1.9, p � 0.001)

Young age(OR 1.6, p � 0.015)

� breast cancer–specific survival; OR � oddsositive.

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Documents

Is Mastectomy Superior to Breast-Conserving Treatment for Young Women?