Eur Radiol DOI 10.1007/s00330-014-3214-x

BREAST

Local recurrence of breast cancer in reconstructed breasts using TRAM flap after skin-sparing mastectomy: clinical and imaging features Hyunkyung Yoo & Bo Hyun Kim & Hak Hee Kim & Joo Hee Cha & Hee Jung Shin & Taik Jong Lee

Received: 19 February 2014 / Revised: 16 April 2014 / Accepted: 2 May 2014 # European Society of Radiology 2014

Abstract Objectives To evaluate clinical and imaging features of cancer recurrence in reconstructed breasts following skin-sparing mastectomy (SSM) or nipple areolar skin-sparing mastectomy (NASSM). Methods This study was approved by our Institutional Review Board. In this retrospective study, we included patients with pathologically confirmed recurrent cancer who had transverse rectus abdominis myocutaneous (TRAM) flap reconstruction after SSM or NASSM and whose follow-up radiological studies were available. Each patient’s demographic data, imaging studies and clinical outcomes were reviewed. Two breast radiologists analysed the imaging findings of follow-up mammography, ultrasound and magnetic resonance imaging. Results Of the 964 patients, 16 (1.7 %) had local cancer recurrence. The average follow-up period until the detection was 31.1 months (range, 7–84 months). Fourteen (87.5 %) patients had recurrence on the skin or in subcutaneous fat. Of the 16 patients, recurrence was detected by breast selfexamination in 13 (81.3 %) patients. Eight (50 %) lesions mimicked benign lesions. The other eight (50 %) lesions manifested various degree of suspicion for the malignancy.

H. Yoo : B. H. Kim : H. H. Kim (*) : J. H. Cha : H. J. Shin Department of Radiology and Research Institute of Radiology, University of Ulsan, College of Medicine, Asan Medical Center, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, South Korea e-mail: [email protected] T. J. Lee Department of Plastic Surgery, Asan Medical Center, University of Ulsan, Seoul, South Korea H. Yoo Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

Conclusions Recurrent cancer after TRAM flap reconstruction following SSM and NASSM is often recognised by breast self-examination and mimics imaging findings of benign lesions. Therefore, meticulous physical examination and history-taking are important. Pathological confirmation is worthwhile even in the benign-appearing lesions. Key Points • Overview of clinical and imaging features of cancer recurrence in reconstructed breasts • 50 % of recurred malignant lesions mimicking imaging findings of benign lesions • Patients may benefit from thorough self-breast examination Keywords Skin-sparing mastectomy . Nipple areolar skin-sparing mastectomy . Transverse rectus abdominis myocutaneous flap reconstruction . Local recurrence of breast cancer

Introduction Breast cancer is one of the most common malignancies in the female population worldwide, and is among the most frequent causes of cancer death. Various surgical methods, including modified radical mastectomy, simple mastectomy, skinsparing mastectomy (SSM) and nipple areolar skin-sparing mastectomy (NASSM) are performed according to the cancer stage and other clinical considerations. Following surgical resection, breast reconstruction is performed for cosmetic reasons. Application of a transverse rectus abdominis myocutaneous (TRAM) flap is a commonly used method of breast reconstruction, which is a standard procedure in autologous breast reconstruction [1, 2]. After mastectomy and breast reconstruction, follow-up studies are carried out for recurrence surveillance. As local recurrences of breast cancer indicate a poor prognosis, they provide important guidelines

Eur Radiol

regarding the management and treatment of these patients. However, there are scarce data regarding the standard protocol for recurrence surveillance after TRAM flap breast reconstruction. Similarly, the roles of the imaging modalities used for follow-up studies are obscure. Several studies [3–7] reported 2-7.5 % local recurrences rates after modified radical mastectomy followed by breast reconstruction. However, as these reports are based only on patients who underwent modified radical mastectomy; they may not reflect the results of newer surgical procedures such as SSM and NASSM. Although the issue of cancer recurrence in reconstructed breast is of significant clinical importance, the detection of recurrence can be challenging. Moreover, there are only a few reports regarding breast cancer recurrence following breast reconstruction and detected on followup studies [3–7]. The purpose of our study is to evaluate clinical and imaging features of cancer recurrence in reconstructed breasts following SSM or NASSM, to discuss the difference in the pattern and rate of cancer recurrence according to the initial stages.

Materials and methods This retrospective study includes all breast reconstruction patients treated at our medical institution from January 2001 to December 2010. The study was approved by our

Institutional Review Board and the need for informed consent was waived. Among the patients, we selected those who initially underwent SSM or NASSM followed by TRAM flap reconstruction. The medical records and database were reviewed for demographic data, past clinical history, imaging studies and clinical outcomes. By searching our medical database, we were finally able to include patients whose followup radiological studies were available for review and whose cancer recurrence was confirmed by surgery or biopsy. Two breast radiologists retrospectively analysed and compared the imaging findings of follow-up studies, including mammography (Senographe DS; General Electric Medical System, Milwaukee, WI, USA), ultrasound (iU22 ultrasound system; Philips Healthcare, Bothell, WA, USA) and magnetic resonance imaging (MRI; Magnetom Avanto; Siemens Healthcare, Erlangen, Germany), which were stored in our generic PACS system. Lesion evaluation and designation were made according to the ACR BI-RADS lexicon of 2003 [8]. We reviewed the records of all patients who underwent TRAM flap reconstruction in order to determining the disease stage at their initial presentation, according to the 2010 American Joint Committee on Cancer Guidelines. We also selectively investigated the initial disease stage in patients with cancer recurrence as well as the type of mastectomy the patient had undergone. At our institution, patients are screened annually by mammography with or without ultrasound according to the clinician’s discretion following surgery. In patients with positive

Table 1 Summary of patients’ information Age

Initial OP

Initial stage

Dx

Symptom

Location

Initial ER/PR/HER2

Current state

35F 32F 33F 42F 52F 33F 51F

NASSM SSM SSM SSM SSM SSM NASSM

I IIb IIa IIa I IIa IIa

IDC IDC IDC IDC IDC IDC IDC

Palpation Palpation Palpation Palpation Palpation (-) (-)

SP SP SP SP SP Chest wall SP

ER(6/7) PR (7/7) Her2(3/3) ER(6/7) PR (0/7) Her2(3/3) ER(6/7) PR (5/7) Her2(0/3) ER(5/7) PR (7/7) Her2(3/3) ER(7/7) PR (7/7) Her2(1/3) ER(0/7) PR (0/7) Her2(3/3) ER(0/7) PR (4/7) Her2(3/3)

CTx, RT, NED lung metastasis CTx, RT, NED Lung, brain metastases CTx, RT, NED CTx, RT, NED bone metastasis

48F 38F 37F 29F 47F 37F 44F 32F 31F

SSM SSM SSM SSM SSM SSM NASSM NASSM NASSM

IIb IIb IIa I I IIa 0 IIb I

IDC IPC IDC IDC IDC IDC DCIS micIDC DCIS

Palpation Palpation (-) Palpation Palpation Palpation Palpation Discharge Discharge

Chest wall SP SP SP SP SP SP SP SP

ER(7/7) PR (6/7) Her2(0/3) ER(0/7) PR (0/7) Her2(0/3) ER(0/7) PR (0/7) Her2(0/3) ER (7/7) PR(4/7) Her2(1/3) ER(0/7) PR(0/7) Her2(1/3) ER(7/7) PR(5/7) Her2(3/3) ER(6/7) PR (7/7) Her2(2/3) ER(3/7) PR (2/7) Her2(3/3) ER(0/7) PR (0/7) Her2(3/3)

CTx, RT, NED CTx, RT, NED regional lymph node metastasis CTx, RT, NED local recurrence (left breast) CTx, RT, NED CTx, RT, NED CTx, RT, NED CTx, RT, NED

OP operation, Dx diagnosis, ER oestrogen receptor, F female, PR progesterone receptor, NASSM nipple and areolar skin sparing mastectomy, SSM skin sparing mastectomy, IDC invasive ductal carcinoma, IPC invasive papillary carcinoma, micIDC microinvasive ductal carcinoma, SP superficial location, CTx chemotherapy, RT radiation therapy, NED no evidence of disease

Eur Radiol Fig. 1 Possible locations of local recurred cancer after TRAM flap reconstruction

BRCA mutation, an additional MRI study is also performed annually.

Results Demographics From January 2001 to December 2010, a total of 993 patients underwent TRAM flap breast reconstruction following various types of mastectomy due to breast cancer. Among them, 581 patients underwent SSM and 383 patients had NASSM. In patients with cancer recurrence, the follow-up period was defined as the time interval until the detection of the recurrence. In patients free of recurrence, the follow-up study results were recorded until March 2012. Of the 964 patients who underwent SSM and NASSM, a total of 16 (1.7 %) patients had local breast cancer recurrence. Lymph node metastasis was detected in eight (0.8 %) patients. The average follow-up period until the detection of local recurrence was 31.1 months (range, 7-84 months). The patients’ information is summarised in Table 1. The sites of local recurrence The sites of local recurrence were classified as superficial layer and deep chest wall related to the location to the TRAM flap. The superficial layer is comprised of skin and subcutaneous fat, including the nipple. Whereas the deep chest wall includes the pectoralis muscle, the intercostal muscles, as well as tissue deeper in the rectus abdominis muscle and used in the TRAM flap. We also investigated recurrence at the TRAM flap itself, the flap margin, in order to describe the recurrence sites in detail. A simplified diagram of the recurrence site is shown in Fig. 1 [9]. The most common site of recurrence was the superficial skin and subcutaneous fat layer, where 14 (87.5 %) patients subsequently had recurrence within the average follow-up period of 32.8 months (Figs. 2 and 3). Among them, two

Fig. 2 A 35-year-old woman underwent nipple and areolar skin sparing mastectomy of the right breast due to invasive ductal carcinoma. The patient complained of a palpable mass in the reconstructed breast. a On mammography (undertaken 8 Sept 2008, 28 Aug 2009 and 8 Sept 2010 respectively from left to right), a well-circumscribed oval nodule with gradual size increase is noticed in the reconstructed breast (arrow). Wide excision of this palpable nodule was performed and recurrent invasive ductal carcinoma was reported. b Ultrasound was performed for the palpable lesion in the reconstructed breast following the mammography. A 0.7-cm benign looking hypo-echoic mass was noticed in the superficial layer

Eur Radiol Fig. 3 A 44-year-old woman underwent nipple and areolar skin sparing mastectomy of the left breast due to invasive ductal carcinoma and concurrent ductal carcinoma in situ. The patient complained of a palpable subareolar mass in the reconstructed breast. a On mammography, a palpable ovoid and well-circumscribed mass is noticed (white dot). b The same lesion on ultrasound revealed an irregular hypo-echoic mass. c On MRI, the lesion is located on the subcutaneous layer of the reconstructed breast (arrow)

patients had recurrence at the nipple (12.5 %). Other recurrence sites included the deep chest wall (two patients, 12.5 %) (Fig. 4). There was no recurrence in the TRAM flap itself or flap margin. The number of patients and the average time to the detection in different recurrence sites are shown in Table 3. In patients who underwent SSM, recurrences in the deep chest wall showed initial stages of IIa and IIb. We investigated the sites of recurrence and their incidence according to mastectomy methods (SSM or NASSM). This result is also summarised in Table 1. Although we only included patients who underwent SSM and NASSM, the recurrence rate was 2.1 % (12/581) and 1.0 % (4/383), respectively. Additionally, the overall stage of all patients who underwent TRAM flap reconstruction and the types of mastectomy in patients with cancer recurrence is shown in Tables 2 and 3.

Fig. 4 A 33-year-old woman underwent skin sparing mastectomy for invasive ductal carcinoma of the right breast. a Two years later, on ultrasound, a 1.1-cm-sized lobulated heterogeneous echoic mass was found within the chest wall. Biopsy revealed recurrent invasive ductal carcinoma (arrow). b PETCT showed a focal hypermetabolic lesion with max SUV of 1.6

Clinical and imaging findings of local recurrent breast cancer after TRAM flap reconstruction In 13 (81.3 %) of the 16 patients, recurrence was detected by breast self-examination. Of these 13 patients, 11 (84.6 %) complained of a palpable mass (Figs. 2 and 3) and two (15.4 %) had nipple discharge or ulceration (Fig. 5). In the other three patients (18.7 %), recurrence was clinically occult and was revealed on routine followup studies (Fig. 4). When the imaging findings of recurrent cancer were reviewed, eight (50 %) lesions demonstrated welldefined, ovoid anechoic to hypo-echoic mass, thus mimicking benign lesions such as a benign mass, cyst or postoperative change. The other eight (50 %) lesions manifested as malignant lesions, showing solid mass with a lobulated contour or internal calcification.

Eur Radiol Table 2 Overall stage of patients who underwent TRAM flap reconstruction Stage (%)

DCIS

I

IIA

IIB

>III

Total

SSM NASSM

106 (18.2) 69 (18.0)

215 (37.0) 138 (36.0)

137 (23.6) 98 (25.6)

64 (11.0) 47 (12.3)

59 (10.2) 31 (8.1)

581 383

DCIS ductal carcinoma in situ, SSM skin sparing mastectomy, NASSM nipple and areolar skin sparing mastectomy

Discussion TRAM flap breast reconstruction after mastectomy is considered to be a safe method that can be performed even in patients with advanced breast cancer. In the literature, the overall incidence of local cancer recurrence following TRAM flap reconstruction is reported to be relatively low, ranging from 2 to 4 % [9, 10]. Also, surgical and medical management of local recurrence are feasible in many patients by means of excision, chemotherapy and radiation therapy [10, 11]. In our study, the recurrence rate was estimated to be 1.7 %, and this result mirrors that of previous reports. With the wide implementation of TRAM flap reconstruction after mastectomy performed for breast cancer, the clinical and radiological detection of cancer recurrence in reconstructed breasts is becoming more and more important. Our study is significant as it describes detailed information regarding different recurrence sites, their incidence and their imaging findings. Noticeably, half of the recurrent cancers mimicked the imaging findings of benign lesions such as cyst or postoperative change. In the other 50 % of all recurrent lesions there were imaging findings of malignancies. In a previous report by Edeiken et al. [12], the imaging features of many (87 %) recurrences were similar to those of primary cancer, and thus demonstrating typical malignant morphology on ultrasound. However, in their study, as some recurrences also had the Table 3 Sites of local recurred breast cancer Site

n (%)

Average times to recurrence detection (months)

Superficial layer TRAM flap itself Deep chest wall

14 (87.5) 0 (0) 2 (12.5)

32.8 19.5

OP margin Total

0 (0) 16 (100)

31.1

OP operation, TRAM transverse rectus abdominis myocutaneous

appearance of benign lesions, ultrasound-guided biopsy was recommended unless the lesion had typical imaging features. Therefore, definitive diagnosis of the lesion by means of biopsy or surgery is very important even in benign-appearing lesion in patients with TRAM flap breast reconstruction. As was demonstrated in our study, the majority of the recurrent lesions were located in the superficial layer of operated breast, including the dermal layer of the native mastectomy flap, and the subcutaneous superficial layer of the TRAM flap. This tendency toward superficial recurrence may be explained by the dermal lymphatic systems of the breast. The centripetal nature of lymphatic drainage in the breast may have transferred tumour cells to the dermal layer of native skin, consequently leading to the proliferation of residual carcinoma in the superficial dermal layer and the subcutaneous fat layer [13–15]. For reference, Hogge et al. [16] reported fat necrosis is frequently located in the reconstructed breast itself as a late complication. Our study shows no recurred lesion at flap itself; thus, this location factor could be helpful to differentiate fat necrosis from recurrence. Due to the superficial location, it is not surprising that recurrence could be detected by the patients’ self-breast examination in more than 80 % of the overall recurrences. A palpable mass was the most common complaint, followed by nipple discharge and ulceration. These results emphasise the importance of self-breast examination and attentive history taking by physicians. Patients may benefit from thorough self-breast examination, and patient education may also increase the efficiency of recurrence detection. In 50 % of the cancer recurrences, the lesions had imaging findings similar to those of benign lesions. Therefore, pathological confirmation is also valuable even when the lesions appear to be benign. Our study has some limitations. First, since we set the end point of follow-up period as March 2012, some patients have not been followed-up long enough to claim recurrence free status of the disease. Additionally, the radiologists only reviewed explorations of patients with known recurrences, and they were aware of this fact. This may have affected the overall recurrence rate in our study, so there is a possibility of

Eur Radiol Fig. 5 A 32-year-old woman with microinvasive ductal carcinoma underwent nipple and areolar skin sparing mastectomy of the left breast. Three years later, the patient had pus-like nipple discharge from the reconstructed breast. Linearly distributing numerous calcifications at the nipple are seen on mammography (a) and ultrasound (b). c On MRI, a 1-cm early enhancing mass is noticed in the left nipple. Wide excision of the nipple and surrounding skin was performed to reveal recurrent ductal carcinoma (Paget’s disease)

the actual recurrence rate being higher than suggested in our study. Second, we did not evaluate the difference in recurrence rates according to the ER/PR/Her-2 status and the pathological subtypes of each cancer. These factors are known to make significant contribution to the recurrence and survival rates. However, the purpose of our study is to provide an overview regarding clinical and imaging features of cancer recurrence in reconstructed breasts after SSM or NASSM, and to suggest an appropriate follow-up imaging protocol.

Also, the current follow-up strategy should be improved, given that it fails to detect the great majority of recurrences, and will need to be studied further.

Acknowledgements The scientific guarantor of this publication is Hak Hee Kim. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was waived by the Institutional Review Board. No study subjects or cohorts have been previously reported. Methodology: retrospective, diagnostic or prognostic study/observational, performed at one institution.

Conclusions Local cancer recurrence after TRAM flap breast reconstruction following SSM and NASSM is usually recognised by patients’ self-examinations, and it often mimics the imaging findings of benign lesions. Therefore, meticulous physical examination and history-taking are important in the detection of recurrence. Radiologists should keep in mind the clinical and imaging features of recurrent breast cancer in TRAM flap reconstructed breasts. Also, pathological confirmation is worthwhile even in benign-appearing lesions, so as to rule out recurrent breast cancer. Although there is no consensus regarding the follow-up protocol for detecting local recurrence, patients are usually scheduled for routine imaging studies according to each medical institution’s policies. However, in our study, as many recurrences were detected only after patients’ developed symptoms, this suggests reconsideration before a blind application of routine follow-up image studies for every patient.

References 1. Hidalgo DA, Borgen PJ, Petrek JA, Heerdt AH, Cody HS, Disa JJ (1998) Immediate reconstruction after complete skin-sparing mastectomy with autologous tissue. J Am Coll Surg 187:17–21 2. Disa JJ, Cordeiro PG, Heerdt AH, Petrek JA, Borgen PJ, Hidalgo DA (2003) Skin-sparing mastectomy and immediate autologous tissue reconstruction after whole-breast irradiation. Plast Reconstr Surg 111:118–124 3. Kroll SS, Khoo A, Singletary SE et al (1999) Local recurrence risk after skin-sparing and conventional mastectomy: a 6-year follow-up. Plast Reconstr Surg 104:421–425 4. Slavin SA, Schnitt SJ, Duda RB et al (1998) Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer. Plast Reconstr Surg 102:49–62 5. Foster RD, Esserman LJ, Anthony JP, Hwang ES, Do H (2002) Skinsparing mastectomy and immediate breast reconstruction: a prospective cohort study for the treatment of advanced stages of breast carcinoma. Ann Surg Oncol 9:462–466

Eur Radiol 6. Carlson GW, Styblo TM, Lyles RH et al (2003) Local recurrence after skin-sparing mastectomy: tumor biology or surgical conservatism? Ann Surg Oncol 10:108–112 7. Medina-Franco H, Vasconez LO, Fix RJ et al (2002) Factors associated with local recurrence after skin-sparing mastectomy and immediate breast reconstruction for invasive breast cancer. Ann Surg 235:814–819 8. American College of Radiology, BI-RADS Committee (2003) ACR BI-RADS breast imaging and reporting data system: breast imaging atlas, 4th edn. American College of Radiology, Reston 9. Langstein HN, Cheng MH, Singletary SE et al (2003) Breast cancer recurrence after immediate reconstruction: patterns and significance. Plast Reconstr Surg 111:712–720, discussion 721-712 10. Howard MA, Polo K, Pusic AL et al (2006) Breast cancer local recurrence after mastectomy and TRAM flap reconstruction: incidence and treatment options. Plast Reconstr Surg 117:1381–1386 11. Lee TJ, Hur WJ, Kim EK, Ahn SH (2012) Outcome of management of local recurrence after immediate transverse rectus abdominis

12.

13. 14. 15.

16.

myocutaneous flap breast reconstruction. Arch Plast Surg 39:376– 383 Edeiken BS, Fornage BD, Bedi DG, Sneige N, Parulekar SG, Pleasure J (2003) Recurrence in autogenous myocutaneous flap reconstruction after mastectomy for primary breast cancer: US diagnosis. Radiology 227:542–548 Handley RS (1964) The early spread of breast carcinoma and its bearing on operative treatment. Br J Surg 51:206–208 Turner-Warwick RT (1959) The lymphatics of the breast. Br J Surg 46:574–582 Suami H, Pan WR, Mann GB, Taylor GI (2008) The lymphatic anatomy of the breast and its implications for sentinel lymph node biopsy: a human cadaver study. Ann Surg Oncol 15:863– 871 Hogge JP, Robinson RE, Magnant CM, Zuurbier RA (1995) The mammographic spectrum of fat necrosis of the breast. Radiographics 15:1347–1356