ORIGINAL RESEARCH

Patients with bilateral breast ductal carcinoma in situ treatedwith accelerated partial breast irradiation—initial experience

Mirna Abboud & Paige Nitsch & Marie Weidman-Johnson &

Mary R. Schwartz & Snehal S. Desai & Sherry Lim &

Darlene M. Miltenburg & Barbara Bass & Bin S. Teh

Received: 17 January 2014 /Accepted: 10 March 2014# Springer-Verlag Berlin Heidelberg 2014

AbstractObjective This study was conducted to report the initial expe-rience of treating patients with synchronous bilateral breastductal carcinomas in situ (DCIS) treated with acceleratedpartial breast irradiation (APBI).Methods Between August 2008 and September 2012, fivepatients with bilateral DCIS were treated with ConturaMulti-Lumen high-dose rate (HDR) brachytherapy to 34 Gyin ten fractions twice daily. The dose was prescribed to 1 cmfrom the applicator surface. We report on the tumor charac-teristics and dosimetric data as well as clinical outcomes andtoxicities according to RTOG 9517 and RTOG 9804. Medianfollow-up was 35 months (range 8–37 months).Results The median age was 61 years (range 61–75). Allpatients had bilateral DCIS. Contralateral DCIS was detectedwith preoperative magnetic resonance imaging (MRI) per-formed before lumpectomy. Median tumor size was 4.8 mmon the right and 10 mm on the left. Two patients had grade 1,one patient had grade 2, and two patients had no acute skintoxicity, respectively. At last follow-up, grade 1 late skintoxicity was reported in two patients, and the remaining

patients did not have any residual skin reaction. Cosmesis wasdescribed as minimal or no difference in the size, shape, ortexture of both breasts. There was no loco-regional recurrence.Conclusion Our initial experience of using APBI to treatbilateral DCIS is safe and effective and associated with excel-lent cosmetic outcome in this small population of patients.Long-term results in a larger population are needed.

Keywords Breast DCIS . APBI . Breast brachytherapy .

Clinical outcomes . Bilateral DCIS

Introduction

Accelerated partial breast irradiation (APBI) has become oneof the treatment options for early stage breast cancer. It is anappealing treatment because of the shortened course (5 days)compared to whole-breast irradiation (6 weeks). In addition,APBI targeting only the tumor bed and adjacent breast tissuesis associated with the potential to reduce radiation toxicity toadjacent organs especially the heart and lungs.

APBI can be delivered using multiple modalities includingmulticatheter interstitial implants placed around the excisioncavity, intraoperative single-dose irradiation, external beamconformal partial breast irradiation, single and multi-lumenballoon catheter as well as strut-adjusted volume implant.Multiple studies have shown equivalent results for APBIcompared to whole-breast external beam radiotherapy [1-3].

Bilateral breast magnetic resonance imaging (MRI) is in-creasingly performed preoperatively for women with breastcancer. In DCIS, MRI has been prospectively shown to have asensitivity of 92 % and up to 98 % for high-grade DCIS [4].Reports on APBI for synchronous bilateral breast cancers arelacking. In this study, we review and report the outcomes offive patients with bilateral breast DCIS treated with APBIusing a multi-lumen catheter.

M. Abboud : P. Nitsch :M. Weidman-Johnson : S. S. Desai :B. S. Teh (*)Department of Radiation Oncology, Houston Methodist Hospital,Cancer Center and Research Institute, 6565 Fannin, Ste #DB1-077,Houston, TX 77030, USAe-mail: bteh@houstonmethodist.org

M. R. SchwartzPathology and Genomic Medicine, Houston Methodist Hospital,Houston, TX, USA

S. Lim : B. BassDepartment of Surgery, Houston Methodist Hospital, Houston, TX,USA

D. M. MiltenburgTexas Women’s Comprehensive Breast Center, Houston, TX, USA

J Radiat OncolDOI 10.1007/s13566-014-0147-6

Methods

Between August 2008 and September 2012, 90 patients weretreated at our Radiation Oncology Department with breast-conserving therapy and adjuvant APBI using the ConturaMulti-Lumen balloon (Hologic®, Marlborough, MA) orstrut-adjusted volume implant (SAVI) device (CiannaMedicalInc, Aliso Viejo, CA). Five patients with bilateral DCIS weretreated with APBI at the same time. High-dose rate brachy-therapy was delivered to a total dose of 34 Gy in ten fractionstwice daily, separated by 6 h daily over 5 days usingIridium 192. The dose was prescribed to 1 cm from theapplicator surface. Median follow-up was 35 months(range 8–37 months).

The patient, tumor, and treatment characteristics(dosimetry) were reviewed. Clinical outcomes and tox-icities were evaluated according to RTOG 9517 andRTOG 9804. With regard to homogeneity of the radia-tion dose within the breast, the volumes of tissue re-ceiving 150 % (V150) and 200 % (V200) of the pre-scribed dose were limited to ≤50 and ≤10 cc, respec-tively. Acute toxicity was defined as toxicity occurringwithin 90 days of the first day of brachytherapy. Latetoxicity was assessed at the day of last follow-up.

Results

Patient and tumor characteristics

Table 1 presents the selected clinical, pathologic, andtreatment-related characteristics of the study population. Themedian age was 61 years (range 61–75). All of the patientswere found to have a breast abnormality on screening mam-mography (three in the right and two in the left breast); a

biopsy was done and pathology was read as DCIS. Eachpatient was determined to be eligible for APBI according tothe NSABP B-39 criteria. All of them qualified for the cau-tionary category according to the American Society for Radi-ation Oncology (ASTRO) consensus statement in view of thepure DCIS histology [32].

MRI was performed on all these patients in order to eval-uate the disease extent and assess for any suspicious areawithin the same or contralateral breast. Breast MRI examina-tions were performedwith the patient in the prone position in a1.5-T system and were able to define contralateral lesions thatwere not visible on mammography.

These lesions were spiculated and demonstrated rapid up-take and rapid washout perfusion kinetics or a plateau type ofenhancement pattern. All of these lesions were biopsy-provenDCIS (Fig. 1).

The patients then underwent bilateral lumpectomies. Onepatient had prominent right axillary lymph nodes on MRI andunderwent a sentinel lymph node biopsy that was negative.

Median tumor size was 4.8 mm on the right and 10 mm onthe left. Median size of the contralateral tumor detected byMRI is 10 mm (range 1.5–29 mm) compared to 4 mm in theindex breast. Three patients had a larger tumor in the contra-lateral breast compared to the index lesion (29 vs. 0.9 mm, 10vs. 4 mm, and 17 mm vs. microscopic disease).

Three patients had positive ER and PR receptors in bothbreasts and two had positive receptors in the left-sided tumorand negative in the right-sided one; Her-2 receptor was per-formed in one patient and was negative. The most commonhistologic subtypes were cribriform and solid patterns. Mar-gins were negative in six out of ten surgical specimens, andthree patients (four specimens) underwent reexcision for pos-itive margins and had negative final margins of at least 2 mm.Seven specimens had a high nuclear grade and three had a lowto intermediate grade by SBR criteria. Two patients received

Table 1 Clinical, pathologic, and treatment-related characteristics

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5

Age 61 75 71 61 61

Pathology DCIS DCIS DCIS DCIS DCIS

Tumor size right (mm) Microscopic 4 29 4.8 6

Tumor size left (mm) 17 10 0.9 30 1.5

ER, PR receptors Positive on 1 side, negativeon the other

Positive Positive Positive on 1 side, negativeon the other

Positive

Her-2 receptors NA NA NA NA Negative

Margins right Negative after reexcision Negative Negative Negative after reexcision Negative

Margins left Negative after reexcision Negative after reexcision Negative Negative Negative

Nuclear grade right 1–2 2 3 3 1

Nuclear grade left 1–2 1 3 1–2 2

Hormonal therapy, yes/no No No Yes No Yes

ER estrogen receptor, PR progesterone receptor, Her-2 human epidermal growth factor-2, DCIS ductal carcinoma in situ, NA not applicable

J Radiat Oncol

hormonal therapy with tamoxifen (one patient) and letrozole(one patient). The rest of the patients with positive ER and PRreceptors refused to take any hormonal treatment. All fivepatients were treated with Contura Multi-Lumen balloon(Hologic®) and received oral antibiotics during the entireradiation course. Table 2 presents the dosimetric parametersin the right and left breast, respectively. These parameters arewithin and better than the initial recommendations from theNational Surgical Adjuvant Breast and Bowel Project(NSABP) studies.

Clinical outcomes

None of the patients developed breast infection. At a medianfollow-up of 35 months, there was no loco-regional recurrence.

Cosmesis was excellent, described as minimal or no differencein the size, shape or texture of both breasts, in all patients.

Side effects

Two patients had grade 1, one patient had grade 2, and two didnot have any acute skin reaction. At a median follow-up of 35months, grade 1 late skin toxicity was reported in two patients,and the remaining patients did not have any residual late skinreaction. There was no symptomatic seroma. One patientdeveloped fat necrosis that was asymptomatic and resolvedspontaneously on subsequent imaging without the need forany intervention.

Discussion

Multiple prospective, randomized controlled trials (RCT)have confirmed the equivalence of lumpectomy pluswhole-breast irradiation (WBI) to modified radical mastec-tomy, in terms of local control, disease-free survival, andoverall survival [5-7]. Breast-conserving therapy (BCT)has become the standard of care for women with earlystage invasive breast cancer. Other studies have evaluatedthe benefit of radiation as a breast conservation componentby comparing lumpectomy alone to lumpectomy and radi-ation therapy. These studies have shown a threefold re-duction in recurrence with the use of radiation therapyfollowing breast-conserving surgery [5, 8-10]. For patientswith DCIS, randomized studies comparing lumpectomyalone to lumpectomy plus radiation therapy found 50 %reduction in the ipsilateral breast cancer events, with theaddition of radiation therapy [11, 12]. Multiple RCTshowed that the majority of local recurrences in the breastof patients who did not receive radiation therapy (RT)occurred at or in the area of the tumor bed. Analysis offailure patterns after BCT utilizing WBI has demonstratedthat between 44 and 86 % of local recurrences occur inthe vicinity of the tumor bed [13-18].

Thus, elective treatment with RT beyond the lumpec-tomy bed may provide minimal additional benefit. In

Fig. 1 T1-weighted MRI images of a patient with bilateral DCIS. Theright breast shows post-biopsy changes (white arrow); in the left breast,there is a 6-mm suspicious lesion that was not detected on mammogramand ultrasound (green arrow)

Table 2 Dosimetric parametersin the right and left breast

PTV planning target volume, Vvolume

Right Left

Average tumor bed-to-skin distance (mm) 7.5 (range 3.6–10) 13.1 (range 6.7–25)

Average PTV volume (cc) 92 91

Average PTVevaluation volume (cc) 73 79

Median maximal skin dose (%) 115 (range 100–128) 106 (range 49–128)

Median maximal rib dose (%) 87 (range 63–133) 105 (range 70–120)

Median V90 (%) 99 99

Median V95 (%) 97 98

Median V100 (%) 93 95

J Radiat Oncol

response to this, a wide variety of accelerated forms ofpartial breast treatment have been developed. These ap-proaches include multicatheter interstitial implants placedaround the excision cavity, external beam conformal partialbreast irradiation, intraoperative single-dose irradiation,single and multi-lumen balloon catheter as well as strut-adjusted volume implant.

One theoretical advantage of APBI is a decreased dose tonormal tissue. Compared to whole-breast radiation, APBItargets a much smaller volume which may lead to a much lessdose to adjacent organs such as the heart and lungs and adecrease in the risk of radiation-induced lung and heart injury[19-21].

The study reports our initial experience of five pa-tients who were treated for bilateral breast DCIS usingbilateral APBI. We only found one case reported byKounalakis et al. in 2011 on a patient with CRESTsyndrome who was treated for bilateral breast cancerswith partial breast irradiation [22]. Our current reportdocuments low rates of toxicities in patients with bilat-eral DCIS treated with APBI using multi-lumen catheterat the same time. This study, with a median follow-upof 35 months, compared favorably to larger studies ofAPBI treating one breast. In the update of theMammosite Breast Brachytherapy Registry Trial, thepercentage of breasts with good/excellent cosmetic re-sults at 60 months (n=371) was 90.6 %. In this trial,2.3 % of the patients developed fat necrosis and thisrate dropped to 0.9 and 0.8 % during years 1 and 2,respectively. The rate of infections was 9.5 %; 98 %occurred during the first year after treatment [23, 24]. Ina report by Brown et al. in 2009 [25], 41 patientstreated with breast-conserving therapy received adjuvantradiation using the Contura catheter. At a medianfollow-up of 8 months, the percentage of patients withexcellent/good cosmetic results was 100 %. Four breastinfections were observed (11 %).

The role of breast MRI in the management of breastcancer patients continues to evolve. We demonstratedthat MRI was able to diagnose contralateral DCIS thatwas not detected on mammography and ultrasound.MRI-detected lesions may be more significant with

APBI than with whole-breast irradiation, given the factthat in APBI, radiation is focused on the lumpectomybed with a 1- to 2-cm margin surrounding the surgicalbed. This will have a more important impact in patientswho are not receiving any systemic or hormonal treat-ment. Contrast-enhanced breast MRI was reported tohave a sensitivity of greater than 90 % in evaluatinginvasive carcinoma. Sensitivities in detecting DCIS arelower, with a range of 40–95 % [26-30]. An occultsecond carcinoma can be identified on MRI in theipsilateral breast in 11–34 % of women with breastcarcinoma [31]. Pathology analyses in mastectomieshave confirmed additional sites of ipsilateral cancer in20–63 % of women and cancer in a different quadrantin 20–47 % [31].

Preoperative breast magnetic resonance imaging (MRI)can be a good tool for detection of ipsilateral and contralateralinvasive tumor foci or ductal carcinoma in situ in addition toclinical examination, mammography, and ultrasonography.Unlike the whole-breast irradiation, APBI does not target themicroscopic tumor cells that can be present in other quadrantsof the breast. Thus, MRI before accelerated partial breastirradiation may help rule out any multifocal or multicentricdisease, remote from the lumpectomy bed, that may convertthe treatment to either modified radical mastectomy or lump-ectomy and whole-breast irradiation. For this reason, ourpatients underwent a preoperative breast MRI.

According to the ASTRO consensus statement, there isinsufficient data to justify recommendation of routine breastMRI for patients selected for APBI [32]. However, multiplestudies have shown that MRI is able to identify additional fociof carcinoma either in the index or even contralateral breast asshown in Table 3. This may lead to a change in the treatmentapproach.

DCIS is assigned to the cautionary category according tothe ASTRO consensus statement [32]. However, APBI isincreasingly used in this group. A large study by Vicini et al.[38] published in 2012 reported the outcomes of 300 patientswith DCIS treated with APBI. The results showed a small rateof ipsilateral breast tumor recurrence (2.6 % at 5 years) withno regional recurrences, which was not different from the ratein the invasive suitable risk group.

Table 3 Various studies addressing the role of MRI in APBI

Study Author Number of patients Additional ipsilateral foci (%) Additional contralateral foci (%)

Dana-Farber [33] Godinez 79 38 Not available

Cleveland Clinic [34] Tendulkar 260 4.2 1.5

German [35] Kühr 113 6.2 1.5

Mayo Clinic in Florida [36] Kowalchik 136 18 4

University of Chicago [37] Dorn 521 11.3 1.6

MRI magnetic resonance imaging, APBI accelerated partial breast irradiation

J Radiat Oncol

Conclusion

To our knowledge, this is the first reported case series ofpatients with bilateral breast DCIS treated with APBI usinga multi-lumen catheter. APBI has been shown not only to befeasible and safe but associated with excellent cosmetic out-comes in this population of patients with bilateral DCIS andMRI-detected contralateral DCIS. Pretreatment breast MRIshould be considered for select patients being treated withAPBI, since MRI may identify patients with occult breastcancer or DCIS away from the index lesion. Defining theexact population of patients who would benefit most frompretreatment breast MRI may require a prospective trial.

Conflict of interest Mirna Abboud, Paige Nitsch, Marie Weidman-Johnson, Snehal Desai, Sherry Lim, Darlene M. Miltenburg, BarbaraBass, and Bin S. Teh declare that they have no conflict of interest.

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