Management of Adenoid Cystic Carcinoma of the Breast: A Rare Cancer Network Study

Int. J. Radiation Oncology Biol. Phys., Vol. 82, No. 5, pp. 2118–2124, 2012Copyright � 2012 Elsevier Inc.

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CLINICAL INVESTIGATION Breast Cancer

MANAGEMENT OFADENOID CYSTIC CARCINOMA OF THE BREAST: A RARECANCER NETWORK STUDY

KAOUTHAR KHANFIR, M.D.,* ADEL KALLEL, M.D.,y SYLVIANE VILLETTE, M.D.,z

YAZID BELKAC�EMI, M.D.,{ CLAIRE VAUTRAVERS, M.D.,x TANDAT NGUYEN, M.D.,**ROBERT MILLER, M.D.,yy YE XIONG LI, M.D.,zz ALPHONSE G. TAGHIAN, M.D., PH.D.,{{

LIESBETH BOERSMA, M.D., PH.D.,xx PHILIP POORTMANS, M.D., PH.D.,*** HADASSAH GOLDBERG, M.D.,yyy

HANSJORG VEES, M.D.,zzz ELZBIETA SENKUS, M.D., PH.D.,{{{ SEFIK IGDEM, M.D.,xxx

MAHMUT OZSAHIN, M.D., PH.D.,xxx AND WENDY JEANNERET SOZZI, M.D.****

*Hopital de Sion, CHCVs, Sion, Switzerland; yInstitut Gustave Roussy, Villejuif, France; zCentre Ren�e Huguenin, Paris, France; {CHUHenri Mondor, Centre Oscar Lambret, Lille, France; xCentre George Francois Leclerc, Dijon, France; **Institut Jean Gaudinot, Reims,France; yyMayo Clinic, Rochester, Minnesota; zzPeking Union Medical College, Beijing, China; {{Massachusetts General Hospital,Boston, Massachusetts; xxMaastricht University Medical Center (MAASTRO clinic), Maastricht, The Netherlands; ***Dr. BernardVerbeeten Institute, Tilburg, The Netherlands; yyyWestern Galilee Hospital-Nahariya, Nahariya, Israel; zzzHopitaux Universitaires deGen�eve, Geneva, Switzerland; {{{Medical University of Gdansk, Gdansk, Poland; xxxIstanbul Bilim University, Istanbul, Turkey; and

****Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Reprindiation OCH-195027 603 45Present

for Thera2009.

Background: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospectivestudy was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC.Methods: Between January 1980 and December 2007, 61 women with breast ACC were treated at participatingcenters of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 pa-tients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to40 patients (35 after lumpectomy, 5 after mastectomy).Results: With a median follow-up of 79 months (range, 6–285), 5-year overall and disease-free survival rates were94% (95% confidence interval [CI], 88%–100%) and 82% (95% CI, 71%–93%), respectively. The 5-year locore-gional control (LRC) rate was 95% (95%CI, 89%–100%). Axillary lymph node dissection or sentinel node biopsywas performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influ-enced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomygroup versus 93% (95% CI, 83%–100%) in the breast-conserving surgery group, respectively (p = 0.16). Forthe breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-yearLRC rates were 95% (95% CI, 86%–100%) for the RT group versus 83% (95% CI, 54%–100%) for the groupreceiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperativeRT.Conclusion: Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillarylymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposedin the case of breast-conserving surgery. � 2012 Elsevier Inc.

Adenoid cystic carcinoma, Breast cancer, Radiotherapy, Surgery.

INTRODUCTION

Adenoid cystic carcinoma (ACC) of the breast is a rare tumortype, with an incidence of less than 0.1% of breast cancers(1–4). It is more frequently reported in the salivary glands(5). Other sites are also reported, including the uterine cervix,Bartholin’s glands, skin, lung, kidney, esophagus, and

t requests to: Kaouthar Khanfir, M.D., Department of Ra-ncology, Hopital de Sion, CHCVs, Grand-Champsec 80,SION, Switzerland. Tel: (+41) 27 603 4522; Fax: (+41)01; E-mail: kaouthar.khanfir@rsv-gnw.ched at the 51st Annual Meeting of the American Societypeutic Radiology and Oncology, Chicago, IL, Nov 1–5,

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prostate (6, 7). These tumors are typically found in womenin the fifth and sixth decades of their lives but can occur inwomen between 19 and 94 years old (1, 3, 4). Typically,ACC presents as a small breast lump 2 to 3 cm in diameter,which has a low propensity to metastasize to regionallymph nodes or distant sites (1–3, 7). Histologically, these

Mahmut Ozsahin and Wendy Jeanneret Sozzi equally contrib-uted equally to this work.Conflict of interest: none.Received Aug 5, 2010, and in revised form Nov 24, 2010.

Accepted for publication Dec 8, 2010.

Table 1. Distribution of ACC patient characteristics

Characteristic No. of patients% of total(n = 61)

Female 61Median age in years and range 59 range, 28–94Median tumor size 20 mm range, 6–170 mmPS0 49 801 12 20

Menopausal statusYes 42 70No 17 27Unknown 2 3

LocalizationUpper outer 26 43Upper inner 10 16Lower inner 5 8Lower outer 4 7Central 11 18Unknown 5 8

UICC T stage classificationT1 30 48T2 24 40T3 3 5T4 4 7

N classificationpN0 84 87cN0 16 13

Estrogen receptor statusNegative 43 71Positive 2 3Unknown 16 26

Progesterone receptor statusNegative 42 69Positive 3 5Unknown 16 26

Abbreviations: PS = performance status; UICC = internationalunion against cancer.

Adenoid cystic carcinoma of the breast d K. KHANFIR et al. 2119

breast tumors are similar to those of ACC of the salivaryglands and are composed of two cell types: myoepithelialcells lining pseudocysts and epithelial cells lining trueglands (8). Because of the rarity of the tumor, there is no con-sensus regarding optimal treatment. Until recently, mastec-tomy has been the classic treatment for breast ACC (1, 4).The aim of this study was to analyze the patterns of failureand outcome in patients treated with surgery with orwithout radiotherapy (RT) and to assess the role of RT.

METHODS AND MATERIALS

PatientsData from 61 patients with ACC of the breast treated between

1980 and 2007 were collected from 16 participating Rare CancerNetwork institutions (www.rarecancer.net). All patients were fe-male, and the median age at diagnosis was 59 years old (range,28–94 years). Seventy percent of the patients were postmenopausal.Most patients had one or more symptoms. A palpable mass was themost common presenting symptom, accounting for 81% of presen-tations. Other symptoms included pain in 14% of the patients. In18% of cases, tumors were first detected on mammography. Therewere 34 right-sided (56%) and 27 (44%) left-sided lesions. The

upper outer quadrant of the breast was the localization most oftenobserved (43%), followed by the central area (18%). No patienthad clinical evidence of regional lymph node and/or distant metas-tases at the time of the initial treatment. A history of malignancywas found in 2 patients (1 patient had had cervical carcinoma insitu, and 1 patient had had breast lymphoma).Preoperative mammography was available in all but 1 case. Stag-

ing investigations, including chest X-rays (n = 53), abdominal ultra-sonography (n = 25), and/or bone scintigraphy (n = 16), wereperformed and showed no evidence of metastatic disease. All pa-tients were classified according to the 2002 International UnionAgainst Cancer (UICC)/American Joint Committee on Cancer(AJCC) classification system (9, 10). For patients treated before2002, staging was updated from previous clinical descriptions tofit the new classifications. There were 30 (49%) stage T1, 24(40%) stage T2, 3 (5%) stage T3, and 4 (6%) stage T4 tumors.Node (N) classifications included 51 (84%) patients with stagepN0 and 10 (16%) patients with stage cN0 disease. All patientsshowed the biphasic cell population of ACC, as defined byQuizilbach et al. (8). In 26% of cases, hormone receptor statuswas not evaluated. Among the remaining 45 patients, 3 (7%) pa-tients had positive results for estrogen receptors (ER), and 2 (5%)patients had positive results for progesterone receptors (PR). Her-2-neu expression analysis was carried out only in the most recentlytreated patients (n = 7), and all tumors were negative. Perineural in-vasion was noted in 5 cases, and 7 tumors were described as poorlycircumscribed. In 1 patient, the tumor was multifocal, and in an-other case it was bifocal. Histologic grading was performed in 12cases (20%) according to the classification described by Bloomand Richardson (11) (i.e., grade 1 in 10 patients, grade 2 in 1 pa-tient, and grade 3 in 1 patient), and none of the patients was gradedaccording to the ACC salivary gland grading system (12). Patientcharacteristics are presented in Table 1.

TreatmentAll patients underwent primary surgery, consisting of lumpec-

tomy in 41 (67%) patients and mastectomy (simple or modified rad-ical mastectomy) in 20 (33%) patients. Surgical margins were closeor positive in 10 (16%) patients, negative in 50 (82%) patients, andunknown in 1 patient (2%). Of these, 9 patients underwent lumpec-tomy and 1 underwent mastectomy, and none of these patients un-derwent re-excision. Axillary lymph node dissection wasperformed in 41 (68%) cases, and 10 (16%) patients underwent sen-tinel lymph node biopsy, which revealed negative lymph nodes inall patients. The median number of lymph nodes examined was 8(range, 1–29).Forty (66%) patients received postoperative RT, and 1 patient

was treated with brachytherapy. The median total dose was 50Gy (range, 45–70.4 Gy) in 25 fractions. Thirty-five patients re-ceived RT to the whole breast after conservative surgery, 17 ofwhom received a follow-up boost irradiation of 10 to 16 Gy withan electron boost field using energy levels of 9 to 15 MeV, and 3other patients received a dose of 20 Gy (range,15–20 Gy) withlow-dose-rate interstitial brachytherapy using iridium-192 wiresaccording to the system described by Dutreix et al. (13). Five ofthe 20 patients treated with mastectomy received chest wall RT. In-dications for RTwere tumor size (T4) in 2 patients, positive marginsin 1 patient, and internal quadrant tumor in 2 patients. Eleven pa-tients received RT to treat draining lymph node areas, including 4patients who underwent mastectomy. The dose per fraction rangedfrom 1.8 to 3 Gy. Only 6 patients received conformal three-dimensional RT. All patients were treated with a linear accelerator,

Fig. 1. Kaplan-Meier curves for OS, DFS, and LRC rates in 61 pa-tients with adenoid cystic carcinoma of the breast.

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except for 5 patients who were treated with a telecobalt machine.One patient was treated with partial breast brachytherapy aloneconsisting of twice-daily treatments using high-dose-rate remoteafterloading iridium-192 to a total dose of 34 Gy in 10 fractions.Fifteen patients received adjuvant systemic (chemo- or hormone)

therapy at the discretion of their treating physician, according to cur-rent evidence showing the advantage of using adjuvant systemictreatment. Four to six cycles of adjuvant chemotherapy weregiven to 8 (13%) patients; chemotherapy regimens consisted of5-fluorouracil-epirubicin-cyclophosphamide (FEC) in 4 patients;cyclophosphamide-methotrexate-5-fluorouracil (CMF) in 2 pa-tients; adoxorubicin-cyclophosphamide (AC) in 1 patient; and unre-corded regimens in 1 cases. Seven other patients receivedprescriptions of tamoxifen.

Statistical analysisMeans were compared using Student’s t test. Proportions were

compared using the chi-square test for values greater than 5, andFisher’s exact test was used for values less than or equal to 5.Kaplan-Meier product limit estimates were used to evaluate overallsurvival (OS), disease-free survival (DFS), and locoregional control(LRC) (14). Time to any event was measured from the date of

Table 2. Patterns of failure in 61 pa

Patient Age (years) Treatment TNM stage Delay (m

1 48 L+AND T2 N0 212 50 L+AND+RT (50Gy) T1cN0 603 48 L T1bNx 994 46 L+AND+RT (66Gy) T1cN0 985 79 M+AND T3 N0 366 42 L+AND+RT+CT T1cN0 97 45 L+ASn+RT (66Gy) T1cN0 198 56 M T4 Nx 20

Abbreviations: L = lumpectomy; AND = axillary node dissection; ASradiotherapy; CT = chemotherapy; TAM = tamoxifen; NED = no eviden* Biopsy proven.

pathology diagnosis. Events were classified as death (all causesof death included) for OS, death or any relapse for DFS, and locore-gional relapse for LRC (patients who died without local or locore-gional relapse were censored at the time of death). Confidenceintervals (CI) were calculated from standard errors. Differences be-tween groups were assessed using the log rank test (15). The Bon-ferroni method was used to adjust individual p values in order toobtain overall significance levels, depending on the number of pa-rameters tested (i.e., with the equation, adjusted p value equals in-dividual p value times the number of parameters tested) (16).Multivariate analyses were performed using Cox stepwise regres-sion analysis (17).

RESULTS

Follow-upThe median follow-up time was 79 months (range, 6–285

months) for all patients.

SurvivalOf the 61 patients in this study, 55 patients lived (6 with

disease, 49 without disease), and 6 patients died: 2 fromACC, 2 from intercurrent disease, and 2 from a secondprimary cancer.

OS, DFS, and LRC curves for the 61 patients are shown inFig. 1. In all patients, the 5- and 10-year OS rates were 94%(95% CI, 88%–100%) and 86% (95% CI, 75%–97%), re-spectively; and DFS rates were 82% (95% CI, 71%–93 %)and 74% (95% CI, 61%–87%), respectively. The 5- and10-year LRC rates were 95% (95% CI, 89%–100%) and87% (95% CI, 76%–98%), respectively.

Patterns of failureTwo of 35 patients treated with lumpectomy and radio-

therapy and 2 of 6 patients treated with lumpectomy aloneexperienced local failure. No local recurrences were ob-served after mastectomy. Time to local relapse ranged be-tween 21 and 99 months. None of the patients hada recurrence within the axilla. Salvage treatment consistedof mastectomy for these four patients, and subsequent lo-coregional control was achieved in all patients. Distant me-tastases occurred in 4 other patients. Time to metastasisranged between 9 and 38 months. At the time of analysis,2 patients died of metastasis (53 and 112 months). Sites of

tients with ACC of the breast

o) Localization Treatment of recurrence

Local Mastectomy (alive and NED)Local Mastectomy (alive and NED)Local Mastectomy (alive and NED)Local Mastectomy (alive and NED)Bone RT (dead for progression, 53 mo later)Liver* CT (alive with disease, 20 mo later)Lung, bone RT-CT (alive with disease, 5 mo later)Lung CT-TAM (dead for progression, 112 mo later)

N = axillary sentinel node; M = mastectomy; mo = months; RT =ce of disease.

Table 3. Univariate analysis of factors influencing DFS in patients with ACC

Characteristic No. of patients 5-year DFS rate (%) 95% CI p valuep value with

Bonferroni correction

All patients 61(N) 82 71–93 – –Age (year)<60 31 76 60–92 0.3 NS$60 26 87 74–100

PS0 49 85 74–96 0.08 NS1 12 64 31–97

Menopausal statusYes 42 85 73–97 0.47 NSNo 17 78 57–99

Clinical T-classificationT1 30 82 66–98 0.27 NST2 24 85 70–100T3 3 0T4 4 75 34–100

Tumor size (mm)<20 26 80 69–95 0.92 NS>20 35 82 63–97

Margin statusNegative 51 81 69–92 0.78 NSClose/positive 10 87 65–100

Surgery typeTumorectomy 35 78 62–93 0.72 NSMastectomy 20 82 65–99Quadrantectomy 6 100

Received RT*Yes 40 80 67–93 0.95 NSNo 21 84 68–100

Estrogen receptor statusPositive 2 50 0–100 0.27 NSNegative 43 82 69–95Unknown 16 84 65–100

Progesterone receptor statusPositive 3 33 0–100 0.002 0.02Negative 42 84 71–97Unknown 16 84 65–100

Perineural invasionYes 5 80 44–100 0.78 NSNo 56 82 71–93

Abbreviations: NS = not significant; PS = performance status; RT = radiotherapy; DFS = disease free survival.* Including 1patient treated with adjuvant brachytherapy.

Adenoid cystic carcinoma of the breast d K. KHANFIR et al. 2121

metastases were lung, bone, and liver. Table 2 summarizesinitial treatments, sites of relapse, salvage therapies, andoutcomes for the 8 patients whose disease relapsed.

Prognostic factorsUnivariate analysis is shown in Table 3. None of the ana-

lyzed variables, i.e., clinical T and N classifications, perfor-mance status, menopausal status, age, or perineural invasion,had a significant influence on DFS. No significant relation-ship was found between DFS and the type of surgery, marginstatus, or use of RT. When we analyzed the relationship be-tween hormone receptor status and DFS, we found that a sig-nificantly better DFS rate was associated with a negative PRstatus (p = 0.002). In multivariate analysis, an improved DFSrate was independently associated with a negative PR status(relative risk [RR] = 6.01� 10�26 [p = 0.004]) and a negativeER status (RR = 7.62 � 10�26 [p = 0.006]).

All local failures occurred in the breast-conservingsurgery group; however, no significant impact of the typeof surgery was seen on the rate of local control (p = 0.16).The 5- and 10-year LRC rates were 100% in the mastectomygroup versus 93% (95% CI, 83%–100%) and 82% (95% CI,65%–99 %) in the breast-conserving surgery group, respec-tively (Fig. 2). The use of RTwas the only factor that signif-icantly correlated with local control in the breast-conservingsurgery group (p = 0.03). The 5- and 10-year LRC rates were83% (95% CI, 54%–100%) and 42% (95% CI, 0%–100%)for the group not treated with RT versus 95% (95% CI,86%–100%) and 88% (95% CI, 73%–100%) for the RT-treated group, respectively (Fig. 3).

If all patients are considered, margin status was not a sig-nificant predictor of local control (p = 0.38), given that allpatients with close/positive margins treated with breast-conserving surgery also received postoperative RT. The

Fig. 2. Comparison of LRC rates according to the mastectomygroup (n = 20) versus the breast- conserving surgery group (n =41) in 61 patients with adenoid cystic carcinoma of the breast(log rank test, p = 0.16).

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5- and 10-year LRC rates were 95% (95% CI, 88%–100%)and 85% (95% CI, 71%–99%) for negative margins, respec-tively, versus 100% for positive margins, respectively.

Of 41 patients treated with conservative surgery, 4 pa-tients had local relapses. All these relapses occurred in 33patients with negative margins. All of the 8 patients withpositive margins received postoperative RT; no local failurewas observed in this group of patients. The 5- and 10-yearLRC rates were 92% (95% CI, 81%–100%) and 76%(95% CI, 54%–98%) for negative margins, respectively,versus 100% for positive margins. (p = 0.29).

Second malignancyFour of 61 (6%) patients developed a second primary can-

cer: 1 patient had contralateral lobular carcinoma, another

Fig. 3. Comparison of LRC rates according to the radiation therapygroup (n = 35) versus the no-radiation-therapy group (n = 6) in 41patients who had breast-conserving surgery for adenoid cystic car-cinoma of the breast (log rank test, p = 0.03).

patient had osteoclast giant-cell tumor, 1 case had bladdercarcinoma, and 1 patient had endometrium carcinoma.None of the second cancers developed in irradiated sites.

DISCUSSION

Results of this study, which was a multiinstitutional expe-rience that included a relatively small sample size from dif-ferent countries of the Rare Cancer Network, confirm thatprimary ACC of the breast is associated with a good progno-sis, with 5- and 10-year OS rates of 94% and 86 % and DFSrates of 82% and 74%, respectively. Five- and 10-year LRCrates were 95% and 87%, respectively. These results areconsistent with those of previous reports (2–4, 7, 18, 19).Moreover, breast ACC has a more favorable prognosisthan breast ductal carcinoma (20).

The natural history and pattern of spread of these tumorsare different from those of classic types of breast cancer, asACC disease is rarely spread by the lymphatic system. In theliterature, the frequency of axillary lymph nodemetastases isestimated to be as low as 0.8%–2% (2, 3). It has beenproposed that lymph node involvement is due to directtumoral extension rather than lymphatic spread (21). No in-volved nodes were seen in the present series of patients inwhom axillary dissection or sentinel lymph node biopsywas performed (84%). Furthermore, none of the cases hada relapse in the axilla, supraclavicular fossa, or internalmammary chain. Results from other studies also supportthe omission of routine axillary lymph node dissection in pa-tients with ACC of the breast (2, 3, 18). Distant metastasesare also rare and range between 0 and 9% (1, 2, 4, 7, 18,19). In the literature, the most common site of metastasisis the lung (1, 3, 12, 22). Other reported sites are liver,kidney, brain, and bone (3, 4, 12, 22). Late-onset metastasisis well known; however, in the present study, the mediantime to metastasis was 20 months, which is shorter thanthat reported in other series. Even with metastatic disease,prolonged survival is common, such as in cases of ACC ofthe salivary glands (1, 2, 23). Those observations werealso confirmed by our findings. Four patients in our studyhad distant failures, and 2 of them died 53 to 112 monthsafter metastases were diagnosed.

Contrary to its salivary gland counterpart, perineural inva-sion is very rarely seen in breast ACC (1, 7). In our study,only 5 patients had perineural invasion, which was notfound to be a prognostic factor.

Hormone assay results of ACC of the breast are typicallyER- and PR-negative, and a Her-2-neu assay does not showamplification (1, 12, 17, 22, 24, 25). Some investigators evensuggest that ER negativity can be used as an indicator toconfirm the pathology diagnosis of ACC (22, 26).Hormone receptor negativity status is not associated witha poor differentiation and a worse prognosis, as seen inductal carcinoma of the breast (22, 24). A differentpathogenesis of breast ACC has already been suggested(18, 27). Hormone receptor-negative cell lineage and nonlu-minal differentiation could explain this negative status in

Adenoid cystic carcinoma of the breast d K. KHANFIR et al. 2123

ACC (22, 27). However, some studies have reported ER-positive incidence rates of 26% to 61%, and PR status wasdescribed as positive in 23% to 36% of tumors (1, 3, 4, 18,19). The significance of the positive hormone receptorstatus is not known. Some authors argue that positivehormone status in these patients may be related to a non-pure ACC or an invasive cribriform carcinoma witha much worse prognosis (24). In the current study, ER- orPR-positive patients showed a poorer outcome. However,our study carries the limitations of a retrospective review,with results that should be interpreted with caution, espe-cially regarding the small number of patients in subgroupanalyses.

Management of ACC of the breast has been mainly surgi-cal, ranging from local excision to radical mastectomy (3, 4).A lack of consensus regarding the optimal management ofACC of the breast has led to global variations in patternsof practice. Mastectomy has been used in 47% to 78% ofpatients (1, 3, 4, 18). Kleer et al. (18) studied 20 patientswith breast ACC and found that the local recurrence ratewas 0% in patients treated with mastectomy versus 11% inthose treated with lumpectomy. Reported recurrence ratesranged from 6% to 37% after local excision (1–4, 18).Arpino et al. (3) reviewed the literature and found that fora total of 182 patients reported in small series or case reports,the local recurrence rate after excision alone was 6% com-pared to 1.5% following mastectomy. Those authors, there-fore, suggest using radiotherapy for local control andavoiding mastectomy (3). Conversely, other investigatorshave advocated local excision as the standard treatment be-cause all local recurrences could be salvaged successfullywith mastectomy (2, 6–8). Indeed in our review, none ofthe relapses occurred in the mastectomy group, and therewas a 5-year actuarial local control rate of 100% versus93% in the breast-conserving surgery group (p = 0.16). Localrelapses had no impact on survival.

Data for the role of RT in breast ACC are limited. There arefew reports containing a substantial number of patients receiv-ing adjuvant RT (3, 4, 6, 7). This is largely because of the rarityof this tumor. Arpino et al. (3) reported a series of 28 patientstreated for breast ACC, the largest study cohort published sofar (3). The authors used postoperative RT in 22% of their pa-tients. No local recurrence was observed. They reporteda slightly more favorable DFS rate than that in our series,

achieving 5- and 10-year DFS rates of 100% and 93.8%, re-spectively. However, in their series, mastectomy was per-formed more frequently than in ours (74% vs. 33%).

Four patients had local relapses in our study. In 2 of thesepatients, the local relapses occurred despite the patients re-ceiving postoperative RT doses of 50 Gy and 60 Gy. Im-proved LRC was associated with the use of RT (p = 0.03)in the breast-conserving surgery group (n = 41), but no im-pact was seen on survival (p = 0.46), as all local failureswere ultimately salvaged successfully. Furthermore, wefound that the status of the resection margin had no influenceon local control. It must be noted that all patients with pos-itive margins received postoperative RT. PostmastectomyRT was used in only 5 patients in this study. It can be pro-posed for positive or close margins.

Millar and coworkers (4) reported their experience with19 patients with breast ACC. Local recurrence-free rateswere 82% and 46% at 5 and 10 years, respectively. Ten pa-tients (52%) underwent breast-conserving surgical treat-ment, and of those, 9 patients also received postoperativeRT, and 8 patients remained disease-free (4). Those authorspropose incorporating postoperative RTas a standard part oftheir treatment. However, in their study, a local recurrencerate was found in the surgery group (5 of 10 patients) thatwas higher than the data presented in the literature (4).They also found late local recurrences. Those findings aresimilar to ours, with 3 of 4 patients having relapses after 5years. Therefore, long-term follow-up is warranted.

CONCLUSIONS

ACC of the breast is a relatively indolent disease with ex-cellent local control and survival outcomes. Axillary lymphnode staging might not be recommended as lymph node me-tastases are extremely rare. Results of breast-conservingtreatment that includes postoperative RT seem to be equiva-lent to those of mastectomy alone, with respect to survival.As all local failures were ultimately salvaged successfully,mastectomy is not justified for small tumors.

Given that in this rare disease, it is practically impossibleto conduct a prospective trial, this study, although retrospec-tive, suggests that postoperative RT should be proposed forall patients after lumpectomy, irrespective of the marginstatus.

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