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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 5  |  Page : 1057-1061

Squamous cell carcinoma of the breast: A retrospective study


Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Web Publication4-Oct-2019

Correspondence Address:
Maher Soliman
Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria 21526
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_303_17

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 > Abstract 


Background: Squamous cell carcinoma (SCC) of the breast is an extremely rare tumor with vague natural behavior and treatment. The purpose of this study was to identify the clinicopathological features and treatment results of this rare type of breast cancer.
Materials and Methods: The medical files of patients with SCC of the breast presented to Alexandria Main University Hospital during the period from January 1990 to January 2010 were retrospectively reviewed, regarding clinicopathological characteristics and treatment outcome and analyzed.
Results: A total of 17 patients were included in this analysis. The median age was 50 years. All patients presented with breast mass. The majority of tumors (88.2%) was negative for hormone receptors. Two-thirds of patients had early T-stage. All patients underwent surgery in our center. Adjuvant tamoxifen was given for two patients. Twelve patients (70.6%) received different adjuvant chemotherapy protocols, and eight patients received radiotherapy. The median disease-free survival was 24 months, and the median overall survival was 40 months. Patients received adjuvant chemotherapy had a statistically significant better disease-free survival (P = 0.014) and overall survival (P = 0.019) compared to patients treated without chemotherapy. Radiotherapy had no significant impact on either disease-free survival or overall survival.
Conclusions: SCC of the breast is a very aggressive tumor, and adjuvant chemotherapy should be strongly considered.

Keywords: Breast cancer, prognosis, squamous


How to cite this article:
Soliman M. Squamous cell carcinoma of the breast: A retrospective study. J Can Res Ther 2019;15:1057-61

How to cite this URL:
Soliman M. Squamous cell carcinoma of the breast: A retrospective study. J Can Res Ther [serial online] 2019 [cited 2019 Oct 20];15:1057-61. Available from: http://www.cancerjournal.net/text.asp?2019/15/5/1057/229635




 > Introduction Top


Squamous cell carcinoma (SCC) of the breast is an extremely rare tumor constituting about 0.075% of all invasive breast cancers.[1],[2] The exact origin and pathogenesis of these neoplasms still remain uncertain. Several pathologic criteria are required to establish a firm diagnosis of SCC of the breast including: the tumor should originate independently from the overlying skin and nipple; more than 90% of the infiltrating component is of squamous type; no other invasive neoplastic elements, ductal, mesenchymal, or otherwise present in the tumor for pure SCC; and other SCC primary sites should be excluded from the study.[1],[3]

Due to the rarity of these tumors and lack of adequate data, the natural behavior for this uncommon malignancy remains controversial. In this report, we try to identify the clinicopathological features and treatment results of this rare type of breast cancer presented to our tertiary center.


 > Materials and Methods Top


In this retrospective study, the medical files of 17 patients with SCC of the breast out of 13,462 patients with breast cancer presented to the clinical oncology department, Alexandria Main University Hospital during the period from January 1990 to January 2010 were reviewed. Data regarding demographic features, clinicopathological characteristics, investigations, primary treatment, adjuvant therapy, and outcome for each case were collected.

Statistical analysis

The analysis was performed using SPSS software version 22 (http://www.ibm.com). The overall survival was calculated from the date of diagnosis to the date of death or last follow-up. Disease-free survival was defined as time from date of diagnosis to date of local recurrence or distant failure, depending on what occurred earlier. Patients without disease recurrence were censored at the last follow-up. Survival curves were calculated using the Kaplan–Meier method and the association between survival and covariates were compared using the two-sided log-rank test. A value of P ≤ 0.05 was considered as statistically significant.


 > Results Top


Patients characteristics

A total of 17 patients were included in this analysis constituting 0.126% of all breast cancer patients presented to our center during the study period. The median age of patients was 50 years (range: 30–63 years). Only one patient (5.9%) had a positive family history. Ten patients (58.8%) were premenopausal. All patients presented by breast mass; one of them had complicated breast abscess; and three patients (17%) had associated axillary swelling at presentation. Only two patients had nipple discharge. Nearly, 15 patients (88.2%) had tumors with negative hormone receptor and the status of human epidermal growth factor receptor 2 (HER2)/neu was available for only seven tumors and all of them were negative. Two-thirds of patients had early T-stage (T1 and T2). The clinical stage was Stage I in three patients, Stage II in seven patients, and Stage III in three patients. Four patients could not be allocated to clinical stage because they had undefined axillae. The left breast (64.7%) was frequently affected compared to the right breast. Around 70% of patients had high-grade tumors (Grade 2 and 3). [Table 1] shows the characteristics of the patients.
Table 1: Patients and disease characteristics of squamous cell carcinoma of the breast

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Treatment

All patients underwent surgery in our center. Radical mastectomy was performed in three patients and modified radical mastectomy was performed for ten cases. Two patients underwent simple mastectomy and another two patients underwent lumpectomy without axillary clearance. Adjuvant tamoxifen was given for two patients with positive hormone receptor tumors. Five patients (29.4%) did not receive adjuvant chemotherapy, while 12 patients (70.6%) received different adjuvant chemotherapy protocols (cyclophosphamide plus methotrexate plus 5-fluorouracil in two patients; cyclophosphamide plus doxorubicin plus 5-fluorouracil in four patients; cisplatinum plus etoposide in three patients; and cisplatinum plus 5-fluorouracil in three patients). About half of cases (eight patients) received adjuvant radiotherapy.

Disease-free survival

About six patients (35.3%) suffered local relapse and eight patients (47%) developed distant metastases. The 5-year disease-free survival rate was 29.3% [Figure 1]a with a median of 24 months (standard error [SE]: 8.92 and 95% confidence interval [CI]: 6.52–41.48). Patients received adjuvant chemotherapy had a statistically significant better disease-free survival compared to those treated without chemotherapy [P = 0.014; [Figure 1]b. Radiotherapy had no statistically significant impact on disease-free survival [P = 0.446; [Figure 1]c. The tumor stage was statistically significantly associated with disease-free survival [P = 0.000; [Figure 2]a.
Figure 1: Disease-free survival rate of patients with squamous cell carcinoma of the breast (a) and the effect of adjuvant chemotherapy (b) and radiotherapy (c)

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Figure 2: Disease-free survival (a) and overall survival (b) rates of patients with squamous cell carcinoma of the breast according to the different clinical stages

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Overall survival

The 5-year overall survival rate was 39% [Figure 3]a with a median of 40 months (SE: 9.97 and 95% CI: 20.45–59.55). Chemotherapy significantly improved the overall survival [P = 0.019; [Figure 3]b. However, radiotherapy had no effect on overall survival [P = 0.926; [Figure 3]c. The tumor stage was significantly correlated with the overall survival [P = 0.000; [Figure 2]b.
Figure 3: Overall survival rate of patients with squamous cell carcinoma of the breast (a) and the effect of adjuvant chemotherapy (b) and radiotherapy (c)

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 > Discussion Top


Primary SCC of the breast constitutes a particularly poorly understood entity of breast cancer with unique biological characteristics. It was first described by Troell in 1908.[4],[5] The incidence of SCC of the breast was reported by Aparicio et al.[2] to be 0.19%. In another study by Cardoso et al.,[6] the incidence was 0.1%. The incidence of SCC of breast fluctuates between 0.06% and 2% in different reports.[7],[8],[9] In this study, it was 0.126% which is within the range.

The median age of patients with SCC at presentation is slightly younger than that of infiltrating ductal carcinoma with a median of 52 years of age.[10],[11] Similar to the literature, the median age of our cases was 50 years. All our cases, presented by breast mass in agreement with literature.[10] In the present study, two-thirds of patients had early T-stage (T1 and T2). Behranwala et al.[1] reported that 63.6% of his patients had early T1 and T2. Approximately 70% of patients with SCC of the breast have no axillary node involvement in axillary dissection.[1],[6] Menes et al.[12] reported that they are associated with a lower rate (22%) of lymph node metastasis and a significant rate of distant metastasis without lymph node involvement. In this study, axillary dissection was performed for thirteen patients and revealed lymph node metastases in three patients which are consistent with the published data.

SCC of the breast usually shows the negativity for estrogen receptor/progesterone receptor (ER/PR) and HER2/neu. However, some reports described rare cases with positive ER/PR.[13],[14] Nair et al.[14] reported a case of SCC with positive ER. In another study, Behranwala et al.[1] found one tumor to be positive for ER out of seven patients assessed in their series. This is consistent with our results, where the majority of tumors (88.2%) were negative for hormone receptors, and only two cases had positive tumors for hormone receptors. HER2/neu is usually negative in SCC of the breast.[13] However, Karamouzis et al.[15] reported a case of HER2/neu-overexpressing SCC. Our cases followed the norm and were negative for HER2/neu.

There is still no consensus regarding the treatment of SCC of the breast. However, it is generally accepted that mastectomy with axillary clearance is the initial treatment.[6],[14],[16] In some cases, especially low-grade small tumors, a lumpectomy with safety margins may be sufficient.[6],[14],[16] All patients underwent surgery in our center. Controversy exists regarding adjuvant therapy. Cisplatinum-based chemotherapy, commonly used for SCC of primary organs other than breast, could be considered for the SCC of the breast.[6],[14],[16] In the current study, chemotherapy significantly increased both disease-free survival and overall survival, in spite of using different adjuvant chemotherapy protocols. To the best of our knowledge, this is the first study to define a significant role of adjuvant chemotherapy in both disease-free survival and overall survival. In contrary to us, Hennessy et al.[16] found no significant difference in the disease-free survival or overall survival rates between the patients treated with adjuvant or neoadjuvant chemotherapy and patients not treated with chemotherapy.

Although SCC of other sites is a relatively radiosensitive tumor, the effectiveness of radiation therapy in this setting has been questioned.[9],[16] In this study, radiotherapy had no significant impact on either disease-free survival or overall survival, though about half of cases received radiotherapy. This agrees with Hennessy et al.[16] who reported that SCC of the breast was relatively radioresistant. However, we suggest to follow the recommendations of infiltrating ductal carcinoma of the breast so far reasonable evidence exists. Hormone therapy has a limited role, as these tumors are usually negative for ER and PR. However, it is reasonable to use endocrine treatment for exceptional cases with ER-and/or PR-positive SCC.[1],[6],[16]

The prognosis of SCC of the breast in published reports is variable due to the limited number of studies, heterogeneous populations, and the small samples size. However, many authors suggest that it is a very aggressive tumor with a tendency to local relapse, progressive invasion, and distant metastasis compared to the usual breast adenocarcinoma.[1],[5],[6],[16] In the current study, the outcomes were also dismal regarding both disease-free survival and overall survival, where a 5-year disease-free survival rate was 29.3% with a median of 24 months, and the 5-year overall survival rate was 39% with a median of 40 months. Consistent with our results, Hennessy et al.[16] reported that the median disease-free survival of 31 patients with localized disease was 20 months; with a 26% disease-free survival rate at 5 years and the median OS in these patients was 37 months; and with 40% surviving at 5 years. Similar to the infiltrating ductal carcinoma of the breast, tumor stage was found to be a significant prognostic factor in this study. This is consistent with the literature.[1],[9],[13],[16] A study by Hennessy et al.[16] found that the stage of the disease was an important prognostic factor for both disease-free and overall survivals. Behranwala et al.[1] reported that both large tumor size and nodal metastases were the principle features of poor prognosis. This was not the case in the studies reported by Aparicio et al.[2] and Cardoso et al.[6] who failed to find a significant effect of tumor size on prognosis. This might be due to the smaller size of their series.

We know that this study has limitations; being a retrospective study with small sample size and different treatment protocols were applied. In spite of these limitations, the present study, to the best of our knowledge is the first report from the Egyptian population and the Middle East area to address this rare cancer. Our data can consolidate and strengthen the literature regarding such very rare cancer, as the rarity of this cancer makes randomized trials impractical.


 > Conclusions Top


SCC of the breast is a very aggressive tumor with unfavorable prognosis. Thus, adjuvant chemotherapy should be strongly considered to improve both disease-free survival and overall survival. Multi-center collaboration, prospective data collection, and further investigations are warranted to explore, understand and optimize the care of SCC of the breast.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Behranwala KA, Nasiri N, Abdullah N, Trott PA, Gui GP. Squamous cell carcinoma of the breast: Clinico-pathologic implications and outcome. Eur J Surg Oncol 2003;29:386-9.  Back to cited text no. 1
    
2.
Aparicio I, Martínez A, Hernández G, Hardisson D, De Santiago J. Squamous cell carcinoma of the breast. Eur J Obstet Gynecol Reprod Biol 2008;137:222-6.  Back to cited text no. 2
    
3.
Macia M, Ces JA, Becerra E, Novo A. Pure squamous carcinoma of the breast. Report of a case diagnosed by aspiration cytology. Acta Cytol 1989;33:201-4.  Back to cited text no. 3
    
4.
Troell A. Zwei Falle von Palttenepithelcarcinom. Nord Med Arkh 1908;1:1-11.  Back to cited text no. 4
    
5.
Moisidis E, Ahmed S, Carmalt H, Gillett D. Primary squamous cell carcinoma of the breast. ANZ J Surg 2002;72:65-7.  Back to cited text no. 5
    
6.
Cardoso F, Leal C, Meira A, Azevedo R, Mauricio MJ, Leal da Silva JM, et al. Squamous cell carcinoma of the breast. Breast 2000;9:315-9.  Back to cited text no. 6
    
7.
Wrightson WR, Edwards MJ, McMasters KM. Primary squamous cell carcinoma of the breast presenting as a breast abscess. Am Surg 1999;65:1153-5.  Back to cited text no. 7
    
8.
Toikkanen S. Primary squamous cell carcinoma of the breast. Cancer 1981;48:1629-32.  Back to cited text no. 8
    
9.
Wargotz ES, Norris HJ. Metaplastic carcinomas of the breast. IV. Squamous cell carcinoma of ductal origin. Cancer 1990;65:272-6.  Back to cited text no. 9
    
10.
Weigel RJ, Ikeda DM, Nowels KW. Primary squamous cell carcinoma of the breast. South Med J 1996;89:511-5.  Back to cited text no. 10
    
11.
Siegelmann-Danieli N, Murphy TJ, Meschter SC, Stein ME, Prichard J. Primary pure squamous cell carcinoma of the breast. Clin Breast Cancer 2005;6:270-2.  Back to cited text no. 11
    
12.
Menes T, Schachter J, Morgenstern S, Fenig E, Lurie H, Gutman H, et al. Primary squamous cell carcinoma (SqCC) of the breast. Am J Clin Oncol 2003;26:571-3.  Back to cited text no. 12
    
13.
Van Hoeven KH, Drudis T, Cranor ML, Erlandson RA, Rosen PP. Low-grade adenosquamous carcinoma of the breast. A clinocopathologic study of 32 cases with ultrastructural analysis. Am J Surg Pathol 1993;17:248-58.  Back to cited text no. 13
    
14.
Nair VJ, Kaushal V, Atri R. Pure squamous cell carcinoma of the breast presenting as a pyogenic abscess: A case report. Clin Breast Cancer 2007;7:713-5.  Back to cited text no. 14
    
15.
Karamouzis MV, Fida A, Apostolikas N, Rigatos G. A case of HER-2(+) squamous cell breast carcinoma: An unusual presentation of an unusual clinical entity. Eur J Surg Oncol 2006;32:1250-1.  Back to cited text no. 15
    
16.
Hennessy BT, Krishnamurthy S, Giordano S, Buchholz TA, Kau SW, Duan Z, et al. Squamous cell carcinoma of the breast. J Clin Oncol 2005;23:7827-35.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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