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Cervical Cancer Metastatic to the Breast: A Case Report and Review of the Literature
Clinical Oncology
Clinical Oncology (1999)11:414–416 # The Royal College of Radiologists
Case Report Cervical Cancer Metastatic to the Breast: A Case Report and Review of the Literature L. Kumar, Y. H. Pokharel, R. Dawar and S. Thulkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India Abstract. Metastasis to the breast from primary cervical cancer is rare. We describe one such patient, who developed breast metastasis 6 months after diagnosis. She was free of pelvic disease at the time of metastases but had evidence of lung involvement. She died of progressive disease 2 months later. Data on 23 patients collected from the literature via Medline are reviewed. Keywords: Breast metastasis; Cervical cancer; Chemotherapy; Radiotherapy
Introduction Extramammary carcinoma metastatic to the breast is uncommon. Frequencies of 0.5%–6.6% have been reported in clinical and autopsy studies. Malignant melanoma, leukaemia/lymphoma, and cancer of the lung, stomach, prostate and ovary are the common primary sites in order of decreasing frequency [1]. Metastasis to the breast from primary cervical cancer is rare. Only 23 cases have been reported in the litereature since 1947. We present a case report of one patient with primary cervical carcinoma who developed breast metastasis and a review of the literature regarding this rare clinical problem.
revealed a smooth vagina with no evidence of a gross lesion or nodularity. Both the parametria were free. Haematological, liver and renal function tests were within normal limits. Chest radiography revealed a left-sided moderate pleural effusion, with multiple, bilateral soft parenchymal opacities widespread in both lung fields (Fig. 1). Mammography showed a single mass with speculated margins in the right upper outer quadrant. There was no evidence of microcalcification (Fig. 2). Magnetic resonance imaging revealed a large, spiculated, well-defined mass in the upper outer
Case Report A 34-year-old woman presented with squamous cell cervical cancer (FIGO Stage IIIB). She underwent a hysterectomy at another hospital, followed by radical pelvic radiotherapy (50 Gy in 26 fractions). She presented to us 5 months later with a 1-month history of a dry cough, left-sided chest pain and breathlessness. Clinical examination revealed a young woman in poor general condition, with an ECOG performance status of 3 and with evidence of a moderate left-sided pleural effusion. In the right breast there was a 5 6 5 cm upper outer quadrant mobile mass, firm to hard in consistency with no evidence of skin tethering or nipple retraction. The left breast was normal. The axillary lymph nodes were not enlarged and there was no evidence of organomegaly or ascites. Pelvic examination Correspondence and offprint requests to: Dr L. Kumar, Associate Professor of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi – 11 00 29, India.
Fig. 1. Chest radiograph showing multiple, diffusely scattered nodular secondaries in both lungs.
quadrant of the right breast, which was hypointense on T1 images and hyperintense on T2 images. There was mild distortion of the architecture around the lesion. No other nodules were seen in either breast. Fine-needle aspiration of the breast mass revealed squamous cell carcinoma with morphological features similar to those of primary cervical cancer. Cytological examination of the pleural fluid was negative for malignant cells on three occasions; however, a pleural biopsy revealed evidence of squamous cell carcinoma. The patient initially underwent pleurodesis using bleomycin 30 units. This was followed by chemotherapy with carboplatin 300 mg/m2, ifosfamide 5 g/m2 and bleomycin 15 mg i.v., all on day 1. She received two cycles at 4-weekly intervals, when there was symptomatic improvement with minimal objective response. However, the patient deteriorated during the next 3 weeks and died at home of progressive disease.
Discussion
Fig. 2. Mammogram: mediastinal view showing dense, welldefined, rounded lesion.
Cervical cancer is the most common cancer among women globally. The disease characteristically spreads contiguously to adjacent structures, to the pelvic and para-aortic nodes by lymphatic dissemination, and to distant organs by a haematogenous route. The reported frequency of distant metastases varies from 38% to 60% in various clinical and autopsy studies, with liver, lung and bone being the most common sites in order of decreasing frequency [2].
Table 1. Literature review Reference
No. patients
Histopathology
FIGO stage
Breast finding
Treatment
Assoc. disease
Comments
McCrea et al. 1983 [1] De Alvarez 1947 [2] Speert and Greeley, 1948 [3]b Badib et al., 1968 [4] Hadju and Ubran, 1972 [5] Nayar et al., 1987 [6] Ward et al., 1989 [7] Singh et al., 1990 [8] Kelly et al., 1991 [9] Younathan et al., 1992 [10] Kumar et al., 1994 [11] Present study
3
NA
NS
Autopsy
NS
NA
NA
1
SCC
NS
Autopsy
NS
DOD
1
SCC
NS
Palpable mass
XRT
4
NS
NS
Autopsy
3
SCC
NS
Palapable mass
3 XRT 1 Surg NS
Widespread disease SCL node (skull) Widespread disease NS
1
IVB
Bilat. masses
None
NS
1
Small cell anaplastic Adeno
IIB
XRT
1
SCC
IIA
Inflammatory lesion Palapable mass
1
Adenosquamous
IB
Palpable mass
Surg + ChT XRT
Cx LNE Ax LNE Skull lytic lesions Ax LNE
DOD
1
SCC
IIB
Palpable mass
XRT
None
NS
1
SCC
IIB
Palpable mass
ChT-XRT
Cx LNE
20 mo survivala
1
SCC
IIIB
Palpable mass
ChT
Cx LNE Pleural effusion
DOD
DOD 4 DOD 2 DOD 1 NK DOD
LFU
a
.Disease-free survival 10 mo. .Referred to four patients described in earlier literature. NA, not available; NS, not stated; SCC, squamous cell carcinoma; Adeno, adenocarcinoma; Adenosquamous, adenosquamous carcinoma; Bilat., bilateral; XRT, external radiotherapy; Surg, surgery; ChT, chemotherapy; SCL, supraclavicular; Cx, cervical; Ax, axillary; LNE, lymph node enlargement; DOD, died of disease; LFU, lost to follow-up. b
Cervical Cancer Metastatic to the Breast
415
Metastasis to the breast is uncommon. In 1948, Speert and Greeley described one patient and could find only four other such cases in the literature [3]. Badib et al. identified four occurrences of breast metastasis among 278 patients with cervical cancer who were studied at autopsy [4]. In a series of 51 patients with metastatic breast cancer reported by Hadju and Ubran, three had primary cervical cancer [5]. McCrea et al. found three cases of cervical cancer among 16 patients with breast metastasis [1]. Nayar et al. reported a patient with small cell anaplastic carcinoma of the cervix with bilateral breast metastases at presentation. This patient had pleural effusion, ascites and lung nodules, and died within 1.5 months of diagnosis [6]. Five more cases have been described in subsequent reports [7–11] (Table 1). Our observation of one such patient among more than 500 women with cervical cancer seen during the past 3 years is similar to these reports. The metastatic spread to the breast has been observed as early as at diagnosis [6] or as late as after 9 years [10]. The exact mechanism of breast metastasis in primary cervical cancer is not known; haematogenous and lymphatic spread have both been suggested. Lymphatic metastasis to the breast can occur via several routes and is dependent upon retrograde flow. One route would be via the subclavian lymph node chain with subsequent back flow to axillary groups, then to subareolar and circumareolar plexuses, finally ending within perilobular and interlobular plexuses within the breast. An alternative route would involve retrograde flow from the anterior parasternal lymph nodes to the medial aspect of the breast [9]. Although the development of solitary or multiple nodules in the breast in known primary cervical cancer suggests metastatic disease, the possibility of primary breast carcinoma should also be kept in mind. The presence of discrete nodules, the lack of fixation to the chest wall, and the absence of skin tethering, peau d’orange, nipple retraction or nipple discharge favour metastatic disease rather than primary breast cancer [10,11]. Mammography may show discrete, well-defined nodules without microcalcification. This is a common appearance for breast metastases [1,11]. There was evidence of widespread disease in the present patient (breast mass, pulmonary metastases, pleural effusion). These observations are similar to earlier reports [4,6] and suggest that breast metastasis is generally associated with widespread disease.
416
L. Kumar et al.
Although in our patient there was no evidence of pelvic recurrence, the initial dose of radiotherapy was less than the usual regimen of 70–80 Gy to point ‘A’ and 60 Gy to point ‘B’. Most of the earlier reports of cervical carcinoma metastatic to the breast are either retrospective clinical or autopsy studies and only limited information is available regarding treatment. In three such reports, patients had an unsuccessful outcome after non-cisplatin chemotherapy [6– 8]. A partial response was obtained using cisplatin alone in one report; after local radiotherapy, one patient survived for more than 20 months [11]. Cisplatin is the most effective drug and should be used for the treatment of metastatic cervical cancer in eligible patients.
References 1. McCrea ES, Johnston C, Haney PJ. Metastasis to breast. Am J Radiol 1983;89:251–6. 2. De Alvarez RR. The causes of death in cancer of cervix uteri. Am J Obstet Gynecol 1947;54:91–6. 3. Speert H, Greeley AV. Cervical cancer metastasis to breast. Am J Obstet Gynecol 1948;55:894–6. 4. Badib AD, Korohara SS, Webster JH, et al. Metastasis to organs in carcinoma of the uterine cervix. Influence of treatment on incidence and distribution. Cancer 1968;21:434–9. 5. Hadju SI, Ubran JA. Cancers metastatic to breast. Cancer 1972;29:1691–6. 6. Nayar M, Chander M, Agrawal R, et al. Carcinoma cervix presenting as a primary breast malignancy. Ind J Pathol Microbiol 1987;3:283–6. 7. Ward R, Connar G, Delprado W, et al. Metastatic adenocarcinoma of the cervix presenting as an inflammatory breast lesion. Gynecol Oncol 1989;35:399–405. 8. Singh K, Chander S, Rath GK, et al. Carcinoma of the uterine cervix metastatic to breast. Report of a case. Ind J Med Sci 1990;44:5–7. 9. Kelly JL, Shakir AK, Williams SL, et al. Cervical cancer metastatic to the breast: a rare presentation of tumor dissemination. Gynecol Oncol 1991;43:291–4. 10. Younathan CM, Steinbach BG, De Bose CD. Metastatic cervical carcinoma to the breast. Gynecol Oncol 1992;45:211–3. 11. Kumar L, Tanwar RK, Karak PK, et al. Breast metastatic from primary cervical cancer. Asia Oceania J Obstet Gynaecol 1994;20:345–8.
Received for publication January 1999 Accepted following revision April 1999
Clinical Oncology (1999)11:414–416 # The Royal College of Radiologists
Case Report Cervical Cancer Metastatic to the Breast: A Case Report and Review of the Literature L. Kumar, Y. H. Pokharel, R. Dawar and S. Thulkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India Abstract. Metastasis to the breast from primary cervical cancer is rare. We describe one such patient, who developed breast metastasis 6 months after diagnosis. She was free of pelvic disease at the time of metastases but had evidence of lung involvement. She died of progressive disease 2 months later. Data on 23 patients collected from the literature via Medline are reviewed. Keywords: Breast metastasis; Cervical cancer; Chemotherapy; Radiotherapy
Introduction Extramammary carcinoma metastatic to the breast is uncommon. Frequencies of 0.5%–6.6% have been reported in clinical and autopsy studies. Malignant melanoma, leukaemia/lymphoma, and cancer of the lung, stomach, prostate and ovary are the common primary sites in order of decreasing frequency [1]. Metastasis to the breast from primary cervical cancer is rare. Only 23 cases have been reported in the litereature since 1947. We present a case report of one patient with primary cervical carcinoma who developed breast metastasis and a review of the literature regarding this rare clinical problem.
revealed a smooth vagina with no evidence of a gross lesion or nodularity. Both the parametria were free. Haematological, liver and renal function tests were within normal limits. Chest radiography revealed a left-sided moderate pleural effusion, with multiple, bilateral soft parenchymal opacities widespread in both lung fields (Fig. 1). Mammography showed a single mass with speculated margins in the right upper outer quadrant. There was no evidence of microcalcification (Fig. 2). Magnetic resonance imaging revealed a large, spiculated, well-defined mass in the upper outer
Case Report A 34-year-old woman presented with squamous cell cervical cancer (FIGO Stage IIIB). She underwent a hysterectomy at another hospital, followed by radical pelvic radiotherapy (50 Gy in 26 fractions). She presented to us 5 months later with a 1-month history of a dry cough, left-sided chest pain and breathlessness. Clinical examination revealed a young woman in poor general condition, with an ECOG performance status of 3 and with evidence of a moderate left-sided pleural effusion. In the right breast there was a 5 6 5 cm upper outer quadrant mobile mass, firm to hard in consistency with no evidence of skin tethering or nipple retraction. The left breast was normal. The axillary lymph nodes were not enlarged and there was no evidence of organomegaly or ascites. Pelvic examination Correspondence and offprint requests to: Dr L. Kumar, Associate Professor of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi – 11 00 29, India.
Fig. 1. Chest radiograph showing multiple, diffusely scattered nodular secondaries in both lungs.
quadrant of the right breast, which was hypointense on T1 images and hyperintense on T2 images. There was mild distortion of the architecture around the lesion. No other nodules were seen in either breast. Fine-needle aspiration of the breast mass revealed squamous cell carcinoma with morphological features similar to those of primary cervical cancer. Cytological examination of the pleural fluid was negative for malignant cells on three occasions; however, a pleural biopsy revealed evidence of squamous cell carcinoma. The patient initially underwent pleurodesis using bleomycin 30 units. This was followed by chemotherapy with carboplatin 300 mg/m2, ifosfamide 5 g/m2 and bleomycin 15 mg i.v., all on day 1. She received two cycles at 4-weekly intervals, when there was symptomatic improvement with minimal objective response. However, the patient deteriorated during the next 3 weeks and died at home of progressive disease.
Discussion
Fig. 2. Mammogram: mediastinal view showing dense, welldefined, rounded lesion.
Cervical cancer is the most common cancer among women globally. The disease characteristically spreads contiguously to adjacent structures, to the pelvic and para-aortic nodes by lymphatic dissemination, and to distant organs by a haematogenous route. The reported frequency of distant metastases varies from 38% to 60% in various clinical and autopsy studies, with liver, lung and bone being the most common sites in order of decreasing frequency [2].
Table 1. Literature review Reference
No. patients
Histopathology
FIGO stage
Breast finding
Treatment
Assoc. disease
Comments
McCrea et al. 1983 [1] De Alvarez 1947 [2] Speert and Greeley, 1948 [3]b Badib et al., 1968 [4] Hadju and Ubran, 1972 [5] Nayar et al., 1987 [6] Ward et al., 1989 [7] Singh et al., 1990 [8] Kelly et al., 1991 [9] Younathan et al., 1992 [10] Kumar et al., 1994 [11] Present study
3
NA
NS
Autopsy
NS
NA
NA
1
SCC
NS
Autopsy
NS
DOD
1
SCC
NS
Palpable mass
XRT
4
NS
NS
Autopsy
3
SCC
NS
Palapable mass
3 XRT 1 Surg NS
Widespread disease SCL node (skull) Widespread disease NS
1
IVB
Bilat. masses
None
NS
1
Small cell anaplastic Adeno
IIB
XRT
1
SCC
IIA
Inflammatory lesion Palapable mass
1
Adenosquamous
IB
Palpable mass
Surg + ChT XRT
Cx LNE Ax LNE Skull lytic lesions Ax LNE
DOD
1
SCC
IIB
Palpable mass
XRT
None
NS
1
SCC
IIB
Palpable mass
ChT-XRT
Cx LNE
20 mo survivala
1
SCC
IIIB
Palpable mass
ChT
Cx LNE Pleural effusion
DOD
DOD 4 DOD 2 DOD 1 NK DOD
LFU
a
.Disease-free survival 10 mo. .Referred to four patients described in earlier literature. NA, not available; NS, not stated; SCC, squamous cell carcinoma; Adeno, adenocarcinoma; Adenosquamous, adenosquamous carcinoma; Bilat., bilateral; XRT, external radiotherapy; Surg, surgery; ChT, chemotherapy; SCL, supraclavicular; Cx, cervical; Ax, axillary; LNE, lymph node enlargement; DOD, died of disease; LFU, lost to follow-up. b
Cervical Cancer Metastatic to the Breast
415
Metastasis to the breast is uncommon. In 1948, Speert and Greeley described one patient and could find only four other such cases in the literature [3]. Badib et al. identified four occurrences of breast metastasis among 278 patients with cervical cancer who were studied at autopsy [4]. In a series of 51 patients with metastatic breast cancer reported by Hadju and Ubran, three had primary cervical cancer [5]. McCrea et al. found three cases of cervical cancer among 16 patients with breast metastasis [1]. Nayar et al. reported a patient with small cell anaplastic carcinoma of the cervix with bilateral breast metastases at presentation. This patient had pleural effusion, ascites and lung nodules, and died within 1.5 months of diagnosis [6]. Five more cases have been described in subsequent reports [7–11] (Table 1). Our observation of one such patient among more than 500 women with cervical cancer seen during the past 3 years is similar to these reports. The metastatic spread to the breast has been observed as early as at diagnosis [6] or as late as after 9 years [10]. The exact mechanism of breast metastasis in primary cervical cancer is not known; haematogenous and lymphatic spread have both been suggested. Lymphatic metastasis to the breast can occur via several routes and is dependent upon retrograde flow. One route would be via the subclavian lymph node chain with subsequent back flow to axillary groups, then to subareolar and circumareolar plexuses, finally ending within perilobular and interlobular plexuses within the breast. An alternative route would involve retrograde flow from the anterior parasternal lymph nodes to the medial aspect of the breast [9]. Although the development of solitary or multiple nodules in the breast in known primary cervical cancer suggests metastatic disease, the possibility of primary breast carcinoma should also be kept in mind. The presence of discrete nodules, the lack of fixation to the chest wall, and the absence of skin tethering, peau d’orange, nipple retraction or nipple discharge favour metastatic disease rather than primary breast cancer [10,11]. Mammography may show discrete, well-defined nodules without microcalcification. This is a common appearance for breast metastases [1,11]. There was evidence of widespread disease in the present patient (breast mass, pulmonary metastases, pleural effusion). These observations are similar to earlier reports [4,6] and suggest that breast metastasis is generally associated with widespread disease.
416
L. Kumar et al.
Although in our patient there was no evidence of pelvic recurrence, the initial dose of radiotherapy was less than the usual regimen of 70–80 Gy to point ‘A’ and 60 Gy to point ‘B’. Most of the earlier reports of cervical carcinoma metastatic to the breast are either retrospective clinical or autopsy studies and only limited information is available regarding treatment. In three such reports, patients had an unsuccessful outcome after non-cisplatin chemotherapy [6– 8]. A partial response was obtained using cisplatin alone in one report; after local radiotherapy, one patient survived for more than 20 months [11]. Cisplatin is the most effective drug and should be used for the treatment of metastatic cervical cancer in eligible patients.
References 1. McCrea ES, Johnston C, Haney PJ. Metastasis to breast. Am J Radiol 1983;89:251–6. 2. De Alvarez RR. The causes of death in cancer of cervix uteri. Am J Obstet Gynecol 1947;54:91–6. 3. Speert H, Greeley AV. Cervical cancer metastasis to breast. Am J Obstet Gynecol 1948;55:894–6. 4. Badib AD, Korohara SS, Webster JH, et al. Metastasis to organs in carcinoma of the uterine cervix. Influence of treatment on incidence and distribution. Cancer 1968;21:434–9. 5. Hadju SI, Ubran JA. Cancers metastatic to breast. Cancer 1972;29:1691–6. 6. Nayar M, Chander M, Agrawal R, et al. Carcinoma cervix presenting as a primary breast malignancy. Ind J Pathol Microbiol 1987;3:283–6. 7. Ward R, Connar G, Delprado W, et al. Metastatic adenocarcinoma of the cervix presenting as an inflammatory breast lesion. Gynecol Oncol 1989;35:399–405. 8. Singh K, Chander S, Rath GK, et al. Carcinoma of the uterine cervix metastatic to breast. Report of a case. Ind J Med Sci 1990;44:5–7. 9. Kelly JL, Shakir AK, Williams SL, et al. Cervical cancer metastatic to the breast: a rare presentation of tumor dissemination. Gynecol Oncol 1991;43:291–4. 10. Younathan CM, Steinbach BG, De Bose CD. Metastatic cervical carcinoma to the breast. Gynecol Oncol 1992;45:211–3. 11. Kumar L, Tanwar RK, Karak PK, et al. Breast metastatic from primary cervical cancer. Asia Oceania J Obstet Gynaecol 1994;20:345–8.
Received for publication January 1999 Accepted following revision April 1999