Multiple metachronous malignancies, one patient with three primary malignancies: a case report
© Fletcher et al; licensee BioMed Central Ltd. 2007
Received: 28 December 2006
Accepted: 02 May 2007
Published: 02 May 2007
We present a 61 year old Para 4 woman who presented with stage II Infiltrating lobular carcinoma of the breast after modified radical mastectomy. She was treated with Tamoxifen for seven years. She was diagnosed with multiple myeloma during year seven post mastectomy because of wrist pain. She was treated with melphalan, prednisone and allopurinol which she tolerated well and the pain in the wrist improved. Tamoxifen was also stopped. Ten months later she presented with vaginal bleeding and was diagnosed with a poorly differentiated endometrial adenocarcinoma at hysteroscopic suction curettage and had an abdominal hysterectomy. Two years later the patient succumbed to metastatic endometrial cancer.
The development of a second primary cancer after treatment of the first with radiotherapy or chemotherapy is well documented . This is often seen with hematological malignancies in childhood where other malignancies, usually haematologic follow, when there is good five year survival .
There are several other reasons for a patient to develop multiple primary malignancies. There may be a genetic predisposition resulting in the cancer family syndrome. The BRCA gene mutation would be one such example. They may also arise as a result of oncogenic viruses such as HPV and HTLV1. DNA damaging toxins are another cause for the development of these malignancies. Exposure to carcinogens can affect different organs at the same time, for example smoking can affect the lungs, nasopharynx and bladder while HPV affects the vulva, vagina and cervix. In some cases they are related to decreased tumour suppression in immunocompromised patients. They may also arise by chance as successful treatment of one malignancy causes prolongation of survival with the possibility of a second one occurring. We present a case of a woman who presented with three primary malignancies over a seven year period.
In December 2001, ten months after stopping the tamoxifen, she was again seen because of an episode of vaginal bleeding which lasted 3 days. The bleeding had been moderate and unprovoked. The history of breast cancer and prolonged tamoxifen use were noted. She had no family history of cancer or of being immunocompromised. and no history of exposure to industrial toxins.
The main risk factor in this patient appears to have been the long term use of the drug tamoxifen. This is a selective estrogen receptor modulator and a known risk of endometrial cancer and sarcomas [2–4]. Tamoxifen is useful as adjuvant treatment of surgically excised breast cancer. It is usually reserved for oestrogen receptor positive breast cancer patients. With its use, recurrence is decreased by 50%, mortality decreased by 28%  and there is a lower incidence of contralateral breast cancer. In one placebo, double blind randomised trial; there was a 49% reduction in breast cancer in high risk women . However since it is not without complication, patients should be informed of the risks which include venous thromboembolism, cataracts and endometrial cancer. The current standard recommendation for use of tamoxifen as adjuvant treatment for breast cancer is 5 years. Use for longer than five years has not been shown to give any added benefit and increases the risk of endometrial cancer . Long term users of tamoxifen also appear to over express the p53 protein on immunohistochemical analysis and this protein is strongly associated with sarcomas and poorly differentiated endometrial carcinomas of the endometrium as was found in this patient who had taken tamoxifen for about seven years . Risk ratio for endometrial cancer is about two and a half to seven times normal in patients being treated with tamoxifen . Non invasive screening procedures such as ultrasonographic endometrial thickness measurement may be beneficial as it has been shown that an endometrial thickness of less than 5 mm is not usually associated with endometrial cancer . However while this has been studied in women with postmenopausal bleeding less is known about it in women on tamoxifen.
The occurrence of the multiple myeloma (MM) appears to have been just a chance event. In this case breast cancer is the most common cancer in Jamaican women Age standardized rate (ASR) 43.2/100,000 (incidence at age 60 173.1/100,000)  and multiple myeloma is common in this age group with a reported incidence of 29.3/100,000 at age 60 years (ASR 3.4/100,000) . Endometrial cancer is also common in this age group reported incidence 50.6/100,000 (ASR 9.8/100,000) . Successful treatment of one cancer will result in the patient living long enough for another age related cancer to arise by chance. This phenomenon has been alluded to in a report from Martinique of adult T cell lymphoma occurring by chance with MM, because in that country HTLV1 (associated with ATL) is endemic and MM is common .
The occurrence of a bone lesion was at first thought to be a metastatic lesion from the breast however her other studies done confirmed MM which required a different treatment which was successful. A second malignancy should be suspected if the bone lesion is atypical or if the blood studies are not in keeping with breast cancer.
The occurrence of the other problems found in this patient may also be linked to her predisposition to malignancy. Oxidative DNA damage is significantly increased in the trabecular meshwork of glaucoma patients. One study found that Genotypes of glutathione S-transferase isoenzymes were significantly higher in glaucoma patients than in controls. Genotypes of glutathione S-transferase iso-enzyme GSTM1 gene deletion, has been associated with an increased risk of cancer at various sites . Unfortunately the genotype of this patient is unknown.
Human T cell Lymphotropic Virus
Human papilloma Virus
Human immunodeficiency Virus
Adult T cell Lymphoma
Glutathione S-transferase iso-enzyme
Haematoxylin and Eosin
We wish to thank the members of staff of Obstetrics and Gynaecology Pathology and Surgery University of the West Indies for their assistance in care of this patient.
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