Keywords
Breast, Endometrium, Cancer, Multiple Primary Malignancy
Breast, Endometrium, Cancer, Multiple Primary Malignancy
Breast cancer (BC) is the most frequently diagnosed malignancy worldwide and is the first cause of cancer death in women1. The common metastatic sites of breast cancer are the lungs, bones, liver and brain. Metastases to the gynecologic and gastrointestinal tract are rare2,3; endometrial cancer (EC) is considered as the most frequent of this type.
Multiple primary malignancy (MPM) has increased over the past decade. It is a term defined as spreading of the primary malignancy to two or more parts of the body distinct from each other. In addition to being distinct, these tumours must have definite featured of malignancy, and the possibility that one is the metastasis of the other must be ruled out4,5. Double primary cancers are the most common types of MPM.
Multiple mechanisms such as hereditary, immune and environmental factors, e.g. chemical, viruses and chemotherapeutic regimens, are considered as the pathogenesis of MPM6. Tumours that are diagnosed simultaneously or within six months are known as synchronous; a longer interval time and the tumours are metachronous.
We present a patient with two primary malignant tumours, including BC (invasive ductal carcinoma) and EC (endometroid cell type), which can be considered as synchronous MPM.
The following case is a 53-year-old woman who was referred to hospital from a local doctor in December 2016 with a palpable mass in her left supraclavicular region. Mammography and chest CT scan revealed the presence of a speculated mass 3.8×3.7 cm in the right breast (Figure 1), and additionally a soft tissue mass 5.8×5.1 cm in the left supraclavicular region (Figure 2). Core needle biopsy for the right breast mass was preformed, and invasive ductal carcinoma with metastatic supraclavicular lymph nodes was confirmed. Although the mass was diagnosed as BC, the patient personally refused to get any treatment. She has a positive family history of breast cancer and uterine cancer in her sister.
An irregular speculated hyperdensity mass in the right breast upper outer quadrant.
A soft tissue mass in the left supraclavicular region consistent with metastatic lymph node (yellow arrow).
One month later, the patient returned with a chief complaint of persistent abnormal vaginal bleeding. She had the history of bleeding 4 years ago and it had worsened over the previous 7 months. Abdominopelvic CT scan of the patient revealed a huge soft tissue mass 14×11 cm in the pelvic cavity with right external iliac and para-aortic lymphadenopathy and dilatation of renal calyces and ureters on both sides (Figure 3).
A soft tissue mass in the pelvic cavity with right external iliac and para-aortic lymphadenopathy.
In January 2017, a total abdominal hysterectomy was performed with no complication, and the pathology revealed EC (with extensive coagulative necrosis and few retained tissue), which had invaded the full thickness of the uterine wall. Pelvic wall mass resection and cervix excision revealed the invasion of the tumour, but peritoneal fluid cytology was negative for malignancy. After two days she discharged from hospital with relative improvement.
We could not follow up the patient because she moved to another city for further treatment; this is one limitation of our study. At the final follow-up, the patient was referred to the oncology department in a different hospital to initiate chemotherapy.
The diagnosis of synchronous primary cancers in an individual is rare and difficult, especially in the case of finding the same type of cancer. In the present case, clinicopathological criteria was used to distinguish the two similar cancers7.
The risk of a new primary cancer in cancer survivors is 20% higher than in the general population8. In addition, it has been was shown that the risk of developing a new malignancy is 1.29 times more than those who have never been diagnosed9. The possibility of synchronous BC and EC in one person is extremely low, as reported in one study the diagnosis of EC within one year after the diagnosis of primary BC is less than 0.05%8.
The coexistence of breast and endometrial cancer reflects the fact that there are many environmental and hormonal risk factors that may predispose the patient to both BC and EC, such as genetics, hormonal, environmental or treatment-related factors, and obesity (i.e. high BMI)10,11. Some of these factors are controversial. For instance, high BMI increases the risk of BC in postmenopausal women; however, it has opposite effect on premenopausal women12,13. By contrast, high BMI increases the risk of EC in both pre and postmenopausal women14,15.
There are many other situations that are correlated with an increasing risk of EC, such as age (i.e. more common in older patients), postmenstrual period16,17, nulliparous, and a positive history of irregular menstrual cycle14. Our case had some of these risk factors, such as being postmenopausal and having a high BMI.
Besides these factors, hormonal status has an important role in endometrial carcinogenesis. Lower exposure to estrogen and higher exposure to progesterone reduce the risk of EC18. The conversion of adrenal hormones into estrogen may be done by fat cells in obese women, so obesity may increase the risk of EC in this way19. Obesity, nullipara and irregular menstrual cycle may represent less progesterone exposure, so they may contribute to EC development. In addition, EC may develop in association with tamoxifen treatment for BC, particularly in the case of long-term administration and high cumulative doses of tamoxifen20–22. The patient in our study did not have any risk factors related to treatment because she did not start BC radio or chemotherapy before presentation of EC symptoms; therefore, we cannot consider the effects of tamoxifen usage in BC as a risk factor of EC in this patient.
Genetic and/or epigenetic changes and other plausible molecular mechanisms might be important in patients with synchronous double cancers23. The present case had a family history of breast and uterine cancer, so heredity could be counted as one of the strongest risk factors for this patient.
In addition to many similar environmental and hormonal risk factors, the same embryological origin of the endometrium and breast can constitute as an additional factor6,24. MPMs can generally be categorized into three major groups depending on the main etiologic factor. The first group are treatment-related neoplasms, the second group are syndromic cases (like Cowden syndrome), and the third group are neoplasms that may share common etiologic factors, such as genetic predisposition or the same environmental factors25. According to this classification, our patient can be categorized in the third group.
To conclude, finding a patient with simultaneous presentation of endometrial and breast cancer is rare; however both of these primary malignancies are considered as the most common cancers in females. Several associated risk factors to this event have been described above. In our case, a high BMI, postmenopausal status and hereditary are probably the most relevant risk factors. Hence, all these factors should be taken into account by clinicians when making a decision concerning screening or strategy for prevention.
Written informed consent for the publication of the patient’s clinical details and images was obtained from the patient.
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Is the background of the case’s history and progression described in sufficient detail?
Partly
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
Partly
Is the case presented with sufficient detail to be useful for other practitioners?
No
Competing Interests: No competing interests were disclosed.
Is the background of the case’s history and progression described in sufficient detail?
Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
Yes
Is the case presented with sufficient detail to be useful for other practitioners?
Yes
Competing Interests: No competing interests were disclosed.
Alongside their report, reviewers assign a status to the article:
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Version 2 (revision) 14 Dec 17 |
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Version 1 17 Aug 17 |
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Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list:
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