Submit Your Article CMED MEACR meeting
Home Print this page Email this page Users Online: 1384
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 4  |  Issue : 6  |  Page : 717-719

Carcinosarcoma of the uterus: Possible sequelae of long-term tamoxifen therapy for breast cancer


1 Department of Radiation Oncology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Gomti Nagar Lucknow, Uttar Pradesh, India
2 Department of Surgical Oncology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Gomti Nagar Lucknow, Uttar Pradesh, India

Date of Web Publication9-Nov-2015

Correspondence Address:
Mohammad Azam
Department of Radiation Oncology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Gomti Nagar, Lucknow - 226 010, Uttar Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-0513.169115

Rights and Permissions
  Abstract 

Carcinosarcoma (CS) of the uterus is rare and accounts for 1–2% of all uterine malignancies, occur commonly in postmenopausal women. These are highly aggressive tumors with poor prognosis and often present at advanced stage. Tamoxifen (TAM) has been known to increase the incidence of endometrial carcinoma from 1 to 2 cases per 1000 women/year and of uterine sarcoma from 0.04 to 0.17 cases per 1000 women/year. TAM has weakly estrogenic properties that can produce endometrial cell proliferation and, consequently, TAM use increases the risk of endometrial cancer by approximately two- to three-fold. Currently, no consensus is present regarding the management of Uterine CS. However, surgery plays an important role in the management along with chemotherapy (CT) and radiotherapy as an adjuvant. We report a case of a woman who developed malignant mixed mullerian tumor of uterus after taking TAM for 6 years as adjuvant hormonal therapy for breast carcinoma.

Keywords: Carcinosarcoma, chemotherapy, radiotherapy, tamoxifen, uterus


How to cite this article:
Azam M, Hadi R, Singhal A, Nanda SS. Carcinosarcoma of the uterus: Possible sequelae of long-term tamoxifen therapy for breast cancer. Clin Cancer Investig J 2015;4:717-9

How to cite this URL:
Azam M, Hadi R, Singhal A, Nanda SS. Carcinosarcoma of the uterus: Possible sequelae of long-term tamoxifen therapy for breast cancer. Clin Cancer Investig J [serial online] 2015 [cited 2019 Oct 23];4:717-9. Available from: http://www.ccij-online.org/text.asp?2015/4/6/717/169115


  Introduction Top


Carcinosarcoma (CS) of the uterus is rare and accounts for 1–2% of all uterine malignancies, with an incidence of <2/100,000 women per year. Uterine CSs are monoclonal tumors classified as malignant mixed mullerian tumor (MMMT), malignant mesodermal mixed tumors, or metaplastic carcinomas.[1] They occur commonly in postmenopausal women and usually present with abdominal pain, distension, and atypical spotting/bleeding per vaginum. These tumors are highly aggressive and often present with extrauterine spread at Stages III–IV with poor prognosis.

Use of tamoxifen (TAM) has been stated to increases the incidence of endometrial carcinoma from 1 to 2 cases per 1000 women per year, and of uterine sarcoma from 0.04 to 0.17 cases per 1000 women per year.

The management of uterine CS has been controversial. However, as a result of its rarity, surgical management has not been well-defined. Literature review by Vorgias et al. in 2010 suggested that the high rates of both local and distant recurrence after surgery essentially need effective adjuvant therapies, although the benefit of adjuvant chemotherapy (CT) or radiotherapy (RT) remains to be determined.

Here, we report a case of woman who developed MMMT of uterus after taking TAM for 6 years as adjuvant hormonal therapy (HT) for breast carcinoma.


  Case Report Top


A 60-year-old postmenopausal para-2 woman presented with complaints of bleeding per vaginum and lower abdominal pain for 2 weeks. On physical examination, there was a palpable pelvic mass. Contrast-enhanced computed tomography (CECT), whole abdomen suggested uterine mass with no appreciable lymph nodes [Figure 1]a and [Figure 1]b.
Figure 1: (a and b) Preoperative contrast-enhanced computed tomography pelvis axial and Sagittal view, respectively, showing large uterine mass without any appreciable lymphadenopathy

Click here to view


Ten years before she was diagnosed as a case of high-grade, hormone-receptor positive (estrogen-receptor positive) invasive carcinoma right breast. She underwent modified radical mastectomy and adjuvant CT and RT. After that, she had taken HT with TAM 20 mg once daily for 6 years.

Total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) was done. Histopathological examination revealed high-grade CS uterus. Six cycles of adjuvant CT with Paclitaxel and Carboplatin was given. Adjuvant RT was given after six cycles of adjuvant CT. Now the patient is on follow-up for 1 year without any evidence of disease on clinical examination, repeat CECT abdomen and positron emission tomography-scan [Figure 2].
Figure 2: Postoperative positron emission tomography, computed tomography scan showing no residual or recurrence lesion

Click here to view



  Discussion Top


Uterine CS is a rare clinical entity, representing <5% of uterine cancer with the median age of presentation is 62 years. There is a very strong association between the TAM treatment and the occurrence of uterine CS. It is evident from the literature that 20 mg/day of TAM over 1 year could be enough to develop uterine sarcoma.[2] Therefore, postmenopausal women taking TAM should be closely monitored for symptoms of endometrial lesions.

CSs are composed of both epithelial and mesenchymal elements. Identification of these two individual components of CSs has led to the concept of their origin.[3] (1) The collision theory, (2) the combination theory, and (3) conversion theory. It is currently believed that CS has a monoclonal origin from a common multidirectional progenitor stem cell, but there remains a percentage of CS with a biclonal origin. An etiological factors implicated in the development of this cancer include prior pelvic exposure to irradiation, obesity, nulliparity, exposure to the human papilloma virus, TAM, and exogenous estrogen.

It is now estimated that 5–30% of patients with CS have a history of pelvic irradiation and is often diagnosed at a latent period of 14 years after irradiation. A typical presentation of CS includes pyometra with vaginal bleeding, watery discharge, abdominal pain, or as a polypoid mass coming out of cervical OS. The "symptom triad" indicative of CS rather than endometrial adenocarcinoma includes pain, severe vaginal bleeding, and the passage of necrotic tissue per vaginum.

Several studies have reported various prognostic factors of uterine CS, including age, stage, lymphovascular space involvement, tumor histology, elevated preoperative CA-125, residual tumor after surgery, positive peritoneal cytology, tumor size, and myometrial invasion.[4] Of patients with localized CS, 20% will be upstaged at laparotomy due to the presence of regional lymph node metastases.[5]

International Federation of Gynecology and Obstetrics staging of MMMTs of the uterus is the same as for endometrial carcinoma. Tumor spread occurs by direct extension to the cervix and vagina followed by other pelvic organs including the bladder and rectum. Lymphatic spread to local and regional lymph nodes appears to occur at an early stage of the disease. Hematogenous spread is also common, usually, to lung, liver, and bone.

Surgery is the cornerstone of treatment, although the extent of the surgical procedure remains unclear. TAH with BSO is the most common procedure; however, the additive benefit of retroperitoneal lymphadenectomy (RLD) remains undetermined.[6] Nemani et al. in 2008

reported a significant overall survival (OS) benefit associated with RLD, with a 5-year OS of 49%, compared with 35% for patients who had not undergone RLD.

The high rates of both local and distant relapse after surgery have warranted the need for effective adjuvant treatment.[7] In a series of cases described by Gonzalez Bosquet et al.,[8] surgery followed by sequential treatment yielded a significantly longer median DFS versus surgery, RT or CT alone. Menczer et al.[9] published a multi-center retrospective study comparing CT with or without radiation to RT alone in patients, who underwent surgical staging. The authors reported that sequential treatment after surgery decreased mortality, as compared to patients taking RT or CT alone. The 5-year OS rate for all stages of uterine CS varies from 10% to 69%.

Historically, ifosfamide has been the most effective CT agent.Recently, phase III trial by Gynecologic Oncology Group (GOG) in 2007 reported that the use of cisplatin plus ifosfamide CT compared favorably over whole abdomino-pelvic radiation as adjuvant therapy in all stages of CS. The results of a recent phase II GOG trial in 2010 suggested that a combination of paclitaxel and carboplatin is also a tolerable and effective regimen.[10]


  Conclusion Top


Uterine CS warrants complete surgical staging and clinical assessment followed by systemic therapy in both early and advanced diseases excluding patients with noninvasive disease. CT is effective in the advanced and metastatic stage of disease. Enough evidence is present to support the use of pelvic radiation and/or vaginal brachytherapy with or without CT for surgical I and II stage patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Arrastia CD, Fruchter RG, Clark M, Maiman M, Remy JC, Macasaet M, et al. Uterine carcinosarcomas: Incidence and trends in management and survival. Gynecol Oncol 1997;65:158-63.  Back to cited text no. 1
    
2.
Arenas M, Rovirosa A, Hernández V, Ordi J, Jorcano S, Mellado B, et al. Uterine sarcomas in breast cancer patients treated with tamoxifen. Int J Gynecol Cancer 2006;16:861-5.  Back to cited text no. 2
    
3.
Jin Z, Ogata S, Tamura G, Katayama Y, Fukase M, Yajima M, et al. Carcinosarcomas (malignant mullerian mixed tumors) of the uterus and ovary: A genetic study with special reference to histogenesis. Int J Gynecol Pathol 2003;22:368-73.  Back to cited text no. 3
    
4.
Garg G, Kruger M, Christensen C, Deppe G, Toy EP. Stage III uterine carcinosarcoma: 2009 International Federation of Gynecology and Obstetrics Staging System and Prognostic Determinants. Int J Gynecol Cancer 2011;21:1606-12.  Back to cited text no. 4
    
5.
Temkin SM, Hellmann M, Lee YC, Abulafia O. Early-stage carcinosarcoma of the uterus: the significance of lymph node count. Int J Gynecol Cancer 2007;17:215-9.  Back to cited text no. 5
    
6.
Sutton G, Kauderer J, Carson LF, Lentz SS, Whitney CW, Gallion H; Gynecologic Oncology Group. Adjuvant ifosfamide and cisplatin in patients with completely resected stage I or II carcinosarcomas (mixed mesodermal tumors) of the uterus: A Gynecologic Oncology Group study. Gynecol Oncol 2005;96:630-4.  Back to cited text no. 6
    
7.
Callister M, Ramondetta LM, Jhingran A, Burke TW, Eifel PJ. Malignant mixed Müllerian tumors of the uterus: Analysis of patterns of failure, prognostic factors, and treatment outcome. Int J Radiat Oncol Biol Phys 2004;58:786-96.  Back to cited text no. 7
    
8.
Gonzalez Bosquet J, Terstriep SA, Cliby WA, Brown-Jones M, Kaur JS, Podratz KC, et al. The impact of multi-modal therapy on survival for uterine carcinosarcomas. Gynecol Oncol 2010;116:419-23.  Back to cited text no. 8
    
9.
Menczer J, Levy T, Piura B, Chetrit A, Altaras M, Meirovitz M, et al. A comparison between different postoperative treatment modalities of uterine carcinosarcoma. Gynecol Oncol 2005;97:166-70.  Back to cited text no. 9
    
10.
Powell MA, Filiaci VL, Rose PG, Mannel RS, Hanjani P, Degeest K, et al. Phase II evaluation of paclitaxel and carboplatin in the treatment of carcinosarcoma of the uterus: A Gynecologic Oncology Group study. J Clin Oncol 2010;28:2727-31.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]


This article has been cited by
1 Tamoxifen
Reactions Weekly. 2016; 1583(1): 1032
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusion
References
Article Figures

 Article Access Statistics
    Viewed3686    
    Printed251    
    Emailed0    
    PDF Downloaded21    
    Comments [Add]    
    Cited by others 1    

Recommend this journal