Abstract
Background/Aim: Areola-sparing mastectomy (ASM), a conservative mastectomy with nipple hollowing, can be applied to intraductal breast cancer with a tumour–nipple-areola complex (NAC) distance of ≤2 cm. Here, we evaluated the safety and effectiveness of ASM. Patients and Methods: We retrospectively reviewed the surgical outcomes of 61 patients (64 breasts) who underwent ASM between 2016 and 2020. Results: Of the 64 breasts, 33 (51.6%) underwent ASM because the tumour–NAC distance on preoperative magnetic resonance imaging was ≤2 cm. Two patients had positive excisional margins but these were at the posterior areola surface therefore additional resection was possible. Over a median postoperative observation period of 16 months (range=3-52 months), one patient developed chest wall recurrence that was resected and did not recur again. Conclusion: For breast cancer with an extensive intraductal component, ASM is a good alternative to nipple-sparing mastectomy because it allows safe resection while maintaining aesthetics.
Breast cancer is a common disease in women, and the incidence of early-stage detection is increasing with the widespread use of mammographic screening (1). With the increase in the incidence of early breast cancer, trends in breast surgery have been towards less invasive and more cosmetically effective methods (2). Halstead’s radical mastectomy was the standard of care until the 1960s (3), following which modified radical mastectomy was performed. Skin-sparing mastectomy (SSM) was first reported by Toth and Lappert; this involves removal of the entire breast parenchyma with the nipple-areola complex (NAC) and preservation of the skin envelope as much as possible (4).
The primary goal of breast cancer surgery is the achievement of local disease control. Moreover, in surgery with reconstruction, achievement of good cosmetic outcomes is an important issue (5, 6). Nipple-sparing mastectomy (NSM) can maximise visual aesthetics. Preservation of the skin envelope and NAC can improve patient satisfaction and provide psychological benefits (7). Although conservative mastectomy has become the standard procedure for many patients with early-stage cancer requesting reconstruction, its use is controversial in terms of oncological safety, and there are no controlled clinical trials evaluating its efficacy (8).
NSM cannot be performed when the tumour is close to the NAC nor when intraductal extension is a concern (9, 10). For safe performance of NSM, it is recommended that the tumour should be at least 2 cm away from the NAC (11). For patients in whom NSM is not indicated, SSM is commonly performed. However, when compared with NSM, SSM has the disadvantage of inferior aesthetics because it leaves a scar on the anterior surface of the breast for NAC removal, followed by the creation of an artificial NAC in two stages.
Areola-sparing mastectomy (ASM), which preserves the entire native skin envelope and areola of the breast, is a surgical technique that falls between SSM and NSM. The greatest advantage of ASM is that it can be used to resect tumours with intraductal extension to the nipple that cannot be resected using NSM while maintaining a good cosmetic appearance (12). However, the history of ASM is short, and there are few reports on its safety and curability (13). At our hospital, ASM has been performed as a highly curative and well-designed technique since 2016. The aim of the present study was to evaluate the safety and effectiveness of ASM for breast cancer with intraductal lesions.
Patients and Methods
Patients. This retrospective study included the data of 1,931 patients who underwent surgery for breast cancer at the Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. From these patients, 1,397 (72.3%) underwent mastectomy, with 80 (5.7%) subjected to NSM and 61 (4.4%) subjected to ASM.
The 61 patients (64 lesions including four synchronous bilateral breast cancers) who underwent ASM were included in our analysis. The Institutional Ethics Committee of the Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital approved all experimental protocols (approval number 2744), and written informed consent was waived because of the retrospective design. The study protocol adhered to the principles of the Declaration of Helsinki and Title 45, U.S. Code of Federal Regulations, Part 46, Protection of Human Subjects, effective December 13, 2001.
Indications for ASM. At our hospital, ASM is indicated for early-stage breast cancer with negative lymph node metastasis that does not require postoperative chest wall irradiation. Preoperative magnetic resonance imaging (MRI) is performed to confirm the extent of the tumour, and mastectomy with or without breast reconstruction is recommended when achievement of radical surgical margins by partial resection is considered difficult. In cases of breast reconstruction, when the distance between the tumour and the nipple exceeds 2 cm, and there is no intraductal extension to the nipple, NSM and ASM are presented as options. However, when the distance between the tumour and NAC is under 2 cm, or if intraductal extension to the nipple is suspected, only ASM is presented as an option (Figure 1). The distance between the tumour and the NAC was measured as the minimum distance between the base of the nipple and the area of contrast on MRI. Positive pathological involvement of the NAC was considered when the tumour or intraductal component was microscopically found within 5 mm from the base of the nipple.
Surgical procedure. The skin incision was made at 9-11 cm on the lateral side of the breast, and the mammary gland was removed up to the subclavian margin on the cranial side, lateral sternal margin on the medial side, and inframammary fold margin on the caudal side. Sentinel node biopsy was performed through the same skin incision on the lateral breast; this allowed an easier approach to the axilla compared with that in SSM, which requires an incision around the NAC. The areola was completely preserved, and the nipple was hollowed out and removed along with the subcutaneous mammary glands. The skin incision around the nipple is basically a circular incision; however, when the cancer is located on the inside of the breast, a transverse or star-shaped incision may be selected. This is because the addition of an incision on the medial part of the areola provides a good view in the medial direction and facilitates skin valve formation (Figure 2). The nipple incision and subcutaneous dissection of the NAC were performed after subcutaneous injection of epinephrine diluted by saline (200,000 times) to prevent bleeding from the rich vascular network. A sharp-edged scalpel was then used to remove the subcutaneous glandular tissue on the posterior surface of the areola, leaving 1-2 mm of the dermis. After removal of all glandular tissue, the nipple resection area was closed, such that a flat nipple was present at the end of the surgery. The nipple was subsequently reconstructed by a plastic surgeon in two stages, using the skin from the areola.
The primary endpoint was curability, assessed by positive margins in pathological evaluation, and the secondary endpoint was local recurrence.
Results
The patient ages ranged from 25 to 79 years (median=45 years), and nipple discharge was observed in five cases. At the start of treatment, as classified by the eighth edition of the American Joint Committee on Cancer staging manual (14), cTis, cT1, and cT2 were observed in 32, 25, and seven cases, respectively, while cN0 and cN1 were observed in 62 and two cases, respectively (Table I). Sixty-two patients with cN0 disease underwent sentinel node biopsy, and three with metastases confirmed by intraoperative rapid diagnosis underwent additional axillary dissection. In addition, two patients with cN1 disease achieved a clinically negative lymph node status after preoperative chemotherapy; therefore, ASM was indicated and axillary dissection was also performed.
All patients underwent preoperative enhanced breast MRI for evaluation of NAC involvement. Patients were almost equally split in regard to the distance between the tumour and the NAC (<2 vs. ≥2 cm) on MRI. ASM was selected for 33 cases where NSM was contraindicated because the distance between the tumour and the NAC was <2 cm. Immediate reconstruction was performed for 55 breasts: Using tissue expander (TE)/implant-based procedures in 35, latissimus dorsi musculocutaneous flap reconstruction in 10, deep inferior epigastric artery perforator flap reconstruction in nine, and deep femoral artery perforator flap reconstruction in one (Table I). Postoperative complications included TE removal due to infection in one case and partial necrosis of the skin flap in three cases; none of these complications were serious.
A positive postoperative pathological margin was observed in two cases of the 61 patients who underwent ASM (3.3%), both of which showed intraductal lesion exposure on the subcutaneous peeled surface of the areola. In both cases, TE reconstruction was performed, and although the areola was additionally excised at the time of implant replacement surgery, no remnant cancer cells were found in the excised specimens. Among the 33 lesions with a tumour–NAC distance of <2 cm on preoperative MRI, 14 (32.6%) showed tumour extension to the nipple or just below the nipple. Conversely, tumour extension to a point just below the NAC was observed in five of 31 (16.1%) cases wherein the tumour–NAC distance was ≥2 cm before surgery (Table II).
The median postoperative observation period was 16 months (range=2-52 months). One patient had a local recurrence in the medial inferior chest wall, which was resected, and no subsequent recurrence has been observed to date.
Discussion
With the increasing number of breast reconstruction procedures, there is a need for surgeries with a high degree of conformity. NSM is the most amenable technique for mastectomy but it is not indicated for patients with suspected tumour extension to the nipple (11).
It is often difficult to accurately diagnose the presence or absence of tumour extension to the NAC before surgery. Intraductal extension to the nipple is suspected in cases where nipple discharge is associated with malignancy, mammography shows calcification near the nipple, and breast MRI shows non-mass enhancement near the nipple (15). However, in some cases, postoperative pathological analysis shows the lesion extending to the nipple in the absence of related symptoms or imaging findings.
Rusby et al. studied patients who underwent SSM and reported that 24.6% patients without tumour extension to the NAC on preoperative imaging had extension in pathological analysis (16). In addition, tumour extension to the NAC has been reported in 11.7-27.7% of NSM cases (17, 18). The tumour–NAC distance measured by MRI is the most important factor in determining the indication for NSM, and it is recommended that patients with a distance of ≥2 cm can undergo NSM in order to ensure safe and complete resection (11, 19). However, even for patients with a distance of <2 cm on preoperative MRI, the rate of pathological nipple involvement was found to be low at 7.5%, with no difference in nipple involvement between patients with a distance of <2 cm from non-mass enhancement and those with a distance of ≥2 cm (20).
Although there is no definitive opinion on the indications for NSM, ASM is considered a good option when there is concern about tumour extension to the nipple. The ASM technique, in which the areola is preserved and only the nipple is removed along with the mammary gland, was reported by Simmons et al. in 2003 (21). Simmons et al. pathologically analysed 217 ASM specimens and found tumour extension to the nipple in 23 (10.6%) cases and to the areola in only two (0.9%) cases; all of these were stage III cases. If the nipple is removed together with the breast parenchyma, complete resection of the lesion extending into the nipple ducts is possible even if the areola is preserved; thus, ASM is an oncologically safe procedure (12, 22).
The NAC comprises 17-27 main milk ducts connected to five to nine openings at the top of the nipple. Some ducts also open into the areolar skin, but their morphology differs from that of the ducts in the nipple, which are reportedly narrow (23). In addition, Montgomery’s glands, which are considered to be sebaceous glands on the areola, are occasionally found to exhibit continuity with milk ducts from the breast parenchyma (24).
Although some nipple ducts are continuous to the areola, most are located in a bundle in the centre of the nipple, and it is reported that 96% of ducts can be removed by excision with 2 mm of the peripheral edge of the nipple (25).
In a microscopic anatomical study of NAC, Rusby et al. showed that removing the ductal bundle in the centre of the nipple and leaving 2 or 3 mm of subcutaneous tissue around the nipple resulted in removal of 96% (2 mm) and 87% (3 mm) of the ductal tissue, respectively. They also reported that leaving 2 or 3 mm of subcutaneous tissue around the nipple would result in preservation of 50% (2 mm) and 66% (3 mm) of the nipple vessels, respectively (23).
Of note, there is often little fat intervening between the areola and mammary gland, and the mammary tissue may be widely adherent directly under the areola. Therefore, the skin incision around the nipple should not be too deep but subcutaneous dissection of the areola from the nipple incision can be performed with a good field of view to minimise residual mammary gland tissue around the NAC.
In contrast, a large amount of mammary gland tissue is left around the NAC in NSM; this is done in order to avoid nipple necrosis. The rate of NAC necrosis in patients undergoing NSM is reportedly 5.9% (8). There is no concern about this complication in ASM, although it is necessary to reconstruct the nipple at a later stage. However, Opsomer et al. (26), using the BREAST-Q, which is one of the most widely used patient-reported outcome measures, reported that patients who underwent ASM had higher scores for “satisfaction with nipple” than did those who underwent SSM and NSM (27).
If the detached edge under the areola is found to be positive in pathological examination, additional excision of the areola at a later stage is necessary; however, the procedure is easy and the wound at the front of the breast is small, so the cosmetic outcome is not significantly inferior to that of SSM. In the present study, both cases with a positive surgical margin below the areola successfully underwent additional resection of the areola under local anaesthesia.
With regard to local recurrence, the cumulative incidence of local recurrence 20 years after conventional mastectomy is reportedly 2.3% (28). Adam et al. also reported an 8-year local recurrence rate of 5% and 7.9% for patients who underwent simple mastectomy and SSM, respectively (29). Furthermore, the rate of recurrence around the NAC in patients treated with NSM is reportedly 2.6-2.7%, although there have been few reports of local recurrence in the long term after ASM, and future reports are awaited (30-32). At our hospital, we found one case of post-ASM recurrence in the inner lower part of the breast that was not associated with the NAC. However, because of the short observation period, long-term follow-up is considered necessary in the future.
In recent years, risk-reducing surgery has been performed for carriers of BRCA DNA repair-associated mutation variants, who are high-risk patients with a genetic predisposition to breast cancer. The percentage of patients undergoing prophylactic NSM has become significantly higher than that of patients undergoing SSM. Manning et al. reported that 21 (6.4%) out of 328 patients who underwent NSM for prophylactic resection were unexpectedly found to have ductal carcinoma in situ, and four of them showed edge positivity and required NAC resection (33). ASM may also be an option for patients scheduled for such prophylactic resections, as it can reduce the likelihood of positive margins.
The present study had some limitations. Firstly, it was a retrospective analysis of data from a single centre and comprised a small number of patients. Secondly, while the natural history of breast cancer involves a long course, the median postoperative observation period was only 16 months, which is a relatively short period. Extensive longitudinal monitoring of patients is needed to determine the precise efficacy of ASM.
In conclusion, ASM may be a reasonable option for patients with contraindications for NSM, as it allows safe resection of cancer while maintaining good cosmesis. The assessment of intraductal extension on preoperative imaging sometimes leads to uncertain results, and ASM is a good indication in cases where there are concerns regarding positive margins. Furthermore, the surgical technique of ASM is easier than that of NSM, and there is no concern regarding NAC necrosis; this reduces the psychological burden on the surgeon as well as the patient. Finally, in cases with a genetic predisposition to breast cancer, ASM could be considered a suitable risk-reducing surgery which is expected to gain popularity in the future.
Acknowledgements
The Authors would like to thank their colleagues at the Department of Breast Surgery and Reconstructive Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital. They would also like to thank Editage (www.editage.com) for English language editing. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Footnotes
Authors’ Contributions
H. Tokisawa contributed to the design and implementation of the research, to the analysis of the results, and H. Tokisawa and T. Aruga contributed to the writing of the article. All Authors discussed the results and commented on the article.
Conflicts of Interest
T. Aruga received honoraria from Chugai Pharmaceutical Co. Ltd., AstraZeneca K.K., Eli Lilly Japan K. K., and Pfizer Japan Inc. The other Authors have no conflicts of interest to declare.
- Received August 12, 2021.
- Revision received October 12, 2021.
- Accepted October 13, 2021.
- Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.