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10.1245/ASO.2005.11.027
Annals of Surgical Oncology 12:1037-1044 (2005)
© 2005 Society of Surgical Oncology
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Original Article

Evaluation of Residual Glandular Tissue After Skin-Sparing Mastectomies

Renato Zocchio Torresan, PhD1, César Cabello dos Santos, PhD1, Hélio Okamura, PhD2 and Marcelo Alvarenga, PhD2

1 Department of Gynecology, Division of Oncology and Senology, State University of Campinas, Av. Alexander Fleming, 101 Cidade Universitária "Zeferino Vaz," Campinas, São Paulo, CEP 13083-881, Brazil
2 Department of Pathology, State University of Campinas, Av. Alexander Fleming, 101 Cidade Universitária "Zeferino Vaz," Campinas, São Paulo, CEP 13083-881, Brazil

Correspondence: Address correspondence and reprint requests to: Renato Zocchio Torresan, PhD; E-mail: torresan{at}terra.com.br


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The oncological safety of skin-sparing mastectomy (SSM) has been the object of several studies.

Methods: From June 2003 to January 2004, 42 breast cancer patients, stage 0 to IIIA, underwent SSM. Before surgery, two lines were drawn on the breast skin, representing SSM and conventional mastectomy incisions. After surgery, the skin flap that would remain after SSM was removed, and immediate breast reconstruction was begun. The presence and amount of remaining glandular breast tissues were histologically evaluated in the skin flap. Terminal ductal lobular units (TDLUs) and residual disease were identified. These data were correlated with other clinical and pathologic parameters by using Fisher’s exact test (P value) and receiver operating characteristic curves.

Results: The prevalence of residual breast tissue in the sample was 59.5%, and the presence of TDLUs was significantly associated with skin flaps thicker than 5 mm. Residual disease was found in 9.5% of the women and was associated with skin flaps >5 mm thick and the presence of TDLUs. There was no significant association between the presence of TDLUs and residual disease with age, body mass index, menopausal status, clinical and pathologic staging, breast volume, mammographic density, neoadjuvant chemotherapy, type of surgery, and presence of an extensive in situ component. The receiver operating characteristic curve showed that as skin flaps decrease in thickness, TDLUs also decrease.

Conclusions: A high prevalence of glandular breast tissue and residual disease in the skin flap was associated with a skin flap thickness >5 mm.

Key Words: Skin sparing • Breast cancer • Mastectomy • Residual glandular tissue


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The skin-sparing mastectomy (SSM) was introduced by Toth and Lappert1 in 1991 to describe a total or radical mastectomy with maximal skin preservation. SSM includes the resection of the nipple/areolar complex, any existing biopsy scar, and the skin overlying the tumor and removal of the entire breast parenchyma. Preservation of the skin envelope of the breast and the inframammary fold provides the reconstructed breast with a more natural shape and contour, thus allowing cosmetic results that are superior to those after conventional mastectomy techniques.2–5 Furthermore, patients require fewer contralateral procedures for symmetry, regardless of the reconstruction technique used.6,7 If dissection between the skin and the breast parenchyma is not performed meticulously, an excess of breast tissue will be left, and this increases the risk of local recurrence (LR) or tumor remaining in the skin.8 However, several studies have shown that SSM is oncologically safe. LR and distant recurrence rates seem similar in comparison of SSM with conventional mastectomies accompanied by immediate breast reconstruction, ranging from 2.0% to 9.5% by 5 years.3,4,9–11 Most of these LRs occur in the skin flap11 and are probably caused by the involvement of dermal lymphatics by tumor cells or direct infiltration of the overlying dermis.12

Because its cosmetic results are superior to those with conventional mastectomy techniques and because oncological equivalence is maintained, SSM has been increasingly used. Initially indicated only for early-stage breast cancer, SSM has been used in cases of locally advanced tumors13 and breast tumor recurrence.14 Recently, changes in the original technique, with preservation of the nipple-areolar complex, which occurs in nipple/areola-sparing mastectomies, have also shown equivalent local disease control, particularly for peripheral and T1 tumors.15,16 However, few studies have been published on the presence of residual glandular breast tissue in the remaining skin, as well as epithelial proliferative findings or residual disease in this tissue.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Forty-two breast cancer patients, stage 0, I, II, or III, without clinical skin involvement, underwent SSM from June 2003 to January 2004 at the Women’s Integral Healthcare Center of the State University of Campinas, Brazil. All patients were verbally instructed about the research design and signed informed consent before surgery. The research protocol was approved by the ethics committee of the institution, according to the ethical principles established in the Helsinki declaration.

Before surgery, two lines on the breast skin were drawn, representing SSM (continuous line) and conventional mastectomy (dotted line) incisions (Fig. 1Go). After SSM, the skin envelope was removed, stretched in a light cardboard, and fixed with pins to avoid retraction, and submitted to histological evaluation (Fig. 2Go). Surgery proceeded, and immediate breast reconstruction was performed with a transverse rectus abdominis musculocutaneous flap or a latissimus dorsi flap with a silicone implant. For each skin flap, minimum and maximum thickness and minimum and maximum width were measured, and 80 glass slides were prepared, stained in hematoxylin and eosin, and examined under an optical microscope. The presence and number of terminal ductal lobular units (TDLUs) were histologically evaluated (Fig. 3Go). Epithelial proliferative findings and residual disease of the TDLUs or dermis were described.


Figure 1
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  		FIG. 1. Native breast skin with conventional mastectomy (dotted line) and skin-sparing mastectomy (continuous line) incisions.

 

Figure 2
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  		FIG. 2. Skin flap after skin-sparing mastectomy stretched in a light cardboard.

 

Figure 3
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  		FIG. 3. Terminal ductal lobular units in the skin flap (Nikon photomicroscope [Nikon Inc., Melville, NY]; original magnification, x25).

 
The association between the presence of TDLUs, residual disease, the thickness of the skin flap, age, body mass index, menopausal status, clinical and pathologic staging, breast volume, mammographic density, neoadjuvant chemotherapy, type of surgery, and the presence of an extensive in situ component was calculated by using Fisher’s exact test. The skin thickness considered for statistical analysis was the thickest area of the inner margin of the skin flap.

To evaluate skin thickness as a continuous parameter, a receiver operating characteristic curve was constructed for each thickness, expressing the relationship between sensitivity and the complement of specificity in the different cutoffs. Data analysis was performed with SAS software (SAS Institute Inc., Cary, NC). A statistically significant difference was obtained at P = .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The characteristics of patients involved in this investigation are listed in Tables 1Go and 2Go. TDLU was present in 25 (59.5%) of 42 patients. Among the parameters studied, only thicker skin flaps were significantly associated with the presence of TDLU.


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  		TABLE 1. Characteristics of patients
 

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  		TABLE 2. Characteristics of patients and association with the presence of TDLUs
 
In 4 (9.5%) of 42 patients, residual disease in the skin flap was found: two invasive ductal carcinomas, one ductal carcinoma-in-situ, and one lobular carcinoma-in-situ. The characteristics of these four cases are listed in Tables 3Go and 4Go. In all these cases, residual disease in the skin flap was significantly associated with the greater number of residual TDLUs and skin flaps thicker than 5 mm. Table 5Go shows that skin flaps >5 mm thick were significantly associated with the presence of TDLU, as well as more TDLUs and residual disease.


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  		TABLE 3. Characteristics of patients with residual neoplasms in the skin flap
 

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  		TABLE 4. Characteristics of patients with residual neoplasms in the skin flap and associations with parameters studied
 

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  		TABLE 5. Association between skin thickness, presence and number of TDLUs, and residual neoplasms
 
The association between skin flap thickness and the presence of TDLU was evaluated by the receiver operating characteristic curve, whose values are graphically expressed in Fig. 4Go. Skin flaps <5 mm thick showed a 28% (7 of 25) rate of TDLU, and as flaps become thinner, the number of residual TDLUs decreased (Table 6Go; Fig. 4Go).


Figure 4
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  		FIG. 4. Receiver operating characteristic curve evaluating skin thickness as a continuous parameter, expressing the relationship between sensitivity and the complement of specificity in the different cutoffs (the cutoff for skin thickness was 5 mm). CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value.

 

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  		TABLE 6. Association between the presence or absence of TDLUs and skin thickness (the cutoff for skin thickness was 5 mm)a
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In this study, more than half of the women who underwent SSM had residual TDLUs in the skin flap, and few had residual disease. The amount of glandular tissue left after mastectomy has been estimated by several authors. In the 1960s, studies conducted on subcutaneous mastectomies showed that this technique removes 85% to 95% of breast tissue.17 In 1973, Goldman and Goldwyn18 performed subcutaneous mastectomies through the inframammary fold in 12 cadavers and found residual glandular tissue in 42%.

Barton et al.,19 after performing biopsies within anatomical mastectomy margins, reported residual glandular tissue in 25% of patients undergoing subcutaneous mastectomy and in 21% of those undergoing radical mastectomy. The material analyzed would represent approximately .2% of glandular volume. Conversely, after SSM, Slavin et al.11 removed strips of skin (1 cm long and .5 cm wide) from the remaining native skin flap edges in 32 patients with early-stage breast cancer, with a total of 114 tissues samples. Histological examination found no ductal breast tissue in the samples collected.

In our study, using a different method than that used by the above-mentioned authors, we showed that after SSM, residual glandular tissue was left in 59.5% of the cases. Operations were performed according to the SSM technique described in previous articles.1–4 To avoid technique variations in our sample, all mastectomies were performed by the two main authors.

As shown in Table 2Go, the presence of this residual glandular tissue was associated with skin flaps thicker than 5 mm. We expected to find more TDLUs in denser breasts, in younger and premenopausal women, and in those with low parity. However, in this study, there was a lack of association between these clinical characteristics related to denser breasts and the presence and number of TDLUs. This fact may have resulted from a small sample size. The calculated patient number (n = 42) was based on the prevalence of TDLUs after mastectomy reported or estimated by other authors.19

Table 5Go demonstrated that thicker flaps were also associated with more glandular residual tissue. Our data also show that as skin flaps become thinner, the likelihood of finding residual glandular tissue in the skin flap is reduced. However, when the flap is too thin, there is a deficit of blood supply, with resulting necrosis and inviability of the skin. Verheyden20 reported that in 20 patients undergoing nipple-sparing mastectomy with 4- to 5-mm-thick skin flaps, mild, moderate, and severe skin necrosis occurred in 16.7%, 6.7%, and 10% of the patients.

Because the cosmetic advantages of SSM are directly correlated with preserving the maximum amount of the breast skin envelope, a challenge faced by the surgeon performing SSM is to preserve the maximum amount of skin with a minimum amount of residual glandular tissue. Some authors recommend that the skin thickness should be approximately 7 to 8 mm,21 and others recommend 2 to 3 mm for thin and 5 to 10 mm for obese patients.22 For Haagensen,23 the optimal dissection plane is just superficial to the superficial layer of the superficial fascia of the breast. However, Beer et al.24 studied 62 breast resection specimens from 31 women undergoing breast-reduction surgery and demonstrated that the superficial fascia was absent in 44% of the material studied. When the fascia was present and homogeneous, there was no glandular breast tissue beyond it. However, in 42% of cases, the fascia was irregular and had various glandular tissue islands. These authors also showed that when the fascia exists, it is not detected macroscopically in most cases. In 50% of patients, the distance from the fascia to the skin is <1.1 mm, regardless of weight and body mass index, thus making visualization of the superficial fascia infeasible as the reference point for the dissection plane.

There is general agreement that if dissection is not meticulously performed between the skin and the breast tissue in SSM, more glandular breast tissue will remain in the skin flap, and, consequently, the theoretical risk of LR is increased.8,10,22 However, LR rates are associated not only with residual glandular tissue left by inadequate surgical techniques, but also with factors such as tumor aggressiveness, tumor size, lack of expression of estrogen receptors, high histological grade, and lymphovascular invasion.25

Therefore, in most patients, glandular tissue is left, but the implications of an increased risk of a new tumor or LR are still unclear. Preservation of the skin envelope in SSM is a cause of concern, because most tumors recur in the skin or subcutaneous tissue (by direct dissemination or lymphatic involvement) and are mostly related to a worse prognosis. Several authors have demonstrated in nonrandomized studies that SSM is oncologically safe when compared with conventional mastectomies accompanied by immediate breast reconstruction, with recurrence rates of approximately 2.0% to 9.5% with an average follow-up of 7 years.3,4,9–11 Medina-Franco et al.,5 in a study of 173 patients undergoing SSM and with a follow-up of 73 months, found a 4.5% LR rate; 75% of patients had metastases and died after 21 months. Retrospectively studying 539 patients with stage 0 to IV disease who underwent SSM with an average follow-up of 65 months, Carlson et al.25 found a 5.5% LR rate, and 77.4% of these patients developed distant disease. Newman et al.,8 in a study of 372 patients, reported an LR rate of 6.2% after local treatment and an average follow-up of 26 months; 61% of the patients were alive with no evidence of disease. In these studies, the authors demonstrated that LR is associated with a worse prognosis and death related to disease. Nevertheless, most cases of LR occurred with more advanced or more aggressive tumors, thus suggesting that local failure may be associated more strongly with tumor biology than with surgical modality.

Conversely, in our study, 4 (9.5%) of 42 cases demonstrated residual disease in the skin after SSM. This residual disease probably could be associated with LR, i.e., related to surgical technique, and not to other important factors, such as staging (Table 4Go). Remaining residual tumor was associated with the thickness of the skin flap and the amount of residual glandular tissue. Studying 30 specimens of total mastectomies in 5-mm sections taken from the site the tumor projected from the skin to a distance 5 cm away, Ho et al.12 found 20% skin involvement. Skin involvement was associated with skin tethering, pathologic tumor size, and perineural infiltration. In these cases, if SSM were indicated and performed, it is likely that high LR rates would be found. The authors concluded that in T1 and T2 tumors, there is a small chance of skin involvement and that in these cases, SSM with preservation of the skin overlying the tumor may be safe.

In conclusion, SSM has been advocated as an oncologically safe procedure for the surgical approach to breast cancer, improving the esthetic results of immediate reconstruction. Recent studies show equivalent rates of local disease control compared to conventional mastectomies, attributing LR to factors related to the biological aggressiveness of the tumor. However, we must consider some aspects concerning the surgical technique, such as the thickness of the skin flap. We found a high prevalence of glandular breast tissue in the skin flap that was associated with skin flaps thicker than 5 mm and with the presence of residual tumor.

Received for publication November 29, 2004. Accepted for publication July 19, 2005.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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