Metachronous Breast Cancer in Patient with Renal Cell Cancer, Experience at National Cancer Institute in Misrata-Libya

Sidoun MA, Elfageih MA, Albolatti KA, Elrgaig MA, Elturki AA, Salah KSB, Elrabie AM, Alansari AH and Alhudhairy EA

Published on: 2021-04-13

Abstract

The occurrence of dual primary cancers is rare, it can be missed as a disease progression. The etiology and possibility of the effect of the antiangiogenesis remain controversial. We report a case of a 41-year-old female with renal cell carcinoma treated with right-sided nephrectomy, after one year of programed follow-up presented with ipsilateral breast mass which was proven after the biopsy to be primary adenocarcinoma of the breast. Any suspicious disease progression in a site not compatible with disease history should be biopsied for confirmation. The relationship between renal cell carcinoma and breast cancer is still unclear, and more case reports are required to determine this relationship.

Keywords

Breast cancer; Renal cell carcinoma; Synchronous; Metachronous; Multiple; Primary; Malignancies; Misrata; Libya

Background

Breast cancer (BC) is common malignancy in women. On the opposite side, renal cell carcinoma (RCC) has the highest rate of all renal malignancy, constituting 2-3% of all cancers in adults [1]. More than one synchronous or metachronous cancer in the same patient is described as multiple primaries. For the purpose of epidemiological studies, tumors are considered to be multiple primary malignancies when they occur at various locations and/or belong to a different histology or morphology group. Depending on the time of diagnosis, synchronous cancers occur simultaneously or within 2 months, while metachronic cancers occur in more than 2 months apart [2]. We report a case of female patient was diagnosed in less than two years with two histologically proved malignancies, RCC with metachronous breast cancer.

Case Presentation

41 year old female patient, her blood group B+, married, known case of hypertension, no history of previous surgery, or previous hospital admission. In January 2018, she was diagnosed as Right RCC with size of 5 cm at the lower pole her computerized tomography (CT) scan showed heterogeneous contrast enhancement lesion with no distant metastasis. Nephrectomy was done. The histopathological diagnosis was clear cell type figure1 with free margin and there was no lymph node involvement or vascular invasion. The patient adviced for post-operative interval follow-up, Adjuvant treatment not needed.

Figure1: The histopathological diagnosis was clear cell type. Hematoxylin and eosin sating (x10).

On June 2019 the patient presented with right outer quadrant breast mass with no bleeding, no skin and nipple retraction, no color change. Ipsilateral and contralateral lymph nodes were negative and contralateral breast was normal at time of examination. Ultrasound results revealed hypoechoic breast mass on the right side (1.2 x 1.5 cm in size) and the BIRAD scale was 4.

Tru cut biopsy was inconclusive, surgical excision performed and histopathological study showed presence of invasive ductal carcinoma IDC with infiltration of resection lines.CT scan was compatible with no distant metastasis. Modified radical mastectomy (MRM) was the treatment of choice and histopathological examination result was compatible with excisional biopsy result was seen IDC in addition to multifocal ductal carcinoma in situ DCIS. Number of lymph node retrieved was 21, all of them were negative with 2 cm free resection margin and Hormone receptor studies were negative for estrogen receptor (ER) and positive for both progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) figure 2. Adjuvant treatment was started after removal of wound stitches, included 6 cycles of chemotherapy (cyclophosphamide, Adriamycin), Herceptin, and tamoxifen. On 11/2019, the patient was completely free of symptoms and signs and blood investigation was within normal limits. Control CECT scan was free of local recurrence and metastasis.

Figure 2: Histopathological examination result was compatible with excisional biopsy result was seen IDC in addition to multifocal ductal carcinoma in situ DCIS. Immunohistochemistry staining showed positive human epidermal growth factor receptor-2 (HER2).

Discussion

Although metastases between BC and RCC may occur, synchronous and metachronous renal and breast tumors are less common [3].Warren and Gates proposed the diagnostic criteria for multiple primary cancers in 1932, namely: (1) Every cancer must be certainly malignant by histopathology, (2) it must be histologically distinct and the risk of metastasizing between cancers must be eliminated [4].

RCC confirmed radiologically in this case, leading to malignant changes in the kidney mass within short period presented with another primary breast cancer. Jayaraman S et al reveled that Multiple metachronous primary cancers are often seen with hematological malignancies of childhood. Exposure to carcinogens like smoking and human papilloma virus may lead to multiple malignancies in the lungs, nasopharynx and urinary bladder, vulva, vagina and uterine cervix [5].

Our patient is 41-year-old, she denied smoking history and was free of any hematological and gynecological malignancies, genetic predisposition and environmental factors, Verkooijen et al found in study population that Breast cancer co-occurrence was pre-treatment with I131 in 35 patients of 282 patients [6].

The etiology of MPM tumors includes interactions between environmental factors (tobacco, occupation, pollution, and ultraviolet light), genetic predisposition as in Li-Fraumeni or Beck-with-Wiedemann Syndrome or Cowden syndrome. the presence of history of side effects with previous chemotherapy and radiotherapy are factors that increase the risk of developing secondary cancers, gender-specific factors and hormonal factors [7-9]. In this current case report, the patient received no radiation either as part of the treatment or as part of previous chemotherapy. Signal transduction, cell proliferation, growth, differentiation, migration and tumor formation play significant roles in HER2 amplification and overexpression. Findings of previous published reports indicate a difference in RCC with respect to the term HER2. The HER2 positive rate in RCC has been reported to be 40 per cent [10]. Here we found overexpressed HER2 receptors in the metachronous breast tumor. Higher incidence of MPM was found in endometrium and ovary associated embryological organs. Organ most often involved in MPM is the breast due to embryological and hormonal factors. Family carcinoma syndrome is a combination of breast and ovary carcinoma [11]. No family history of cancer was reported in our patient and also there was no known risk factors for the above mentioned diseases.

Breast metastases are very rare in comparison to primary tumours. Breast is the least RCC metastasis site [12]. No histological and immune stain characteristics in the MRM specimen of the reported patient, make it incompatible with breast metastasis of renal cancer. Personalized and special care in synchronous tumors is determined after proper evaluation at multidisciplinary team meetings and consensus on a therapeutic strategy. Neoadjuvant chemotherapy was Started as a treatment for synchronous tumors in local advanced cancer, While the therapeutic course involves the sequential treatment of each individual tumor in metachronous tumors [13,14] , in our case nephrectomy for RCC performed as first occurrence, then modified radical mastectomy performed to the invasive ductal carcinoma as the second metachronous.

In a survey of over 1,425 patients with RCC, Beisland, Talleraas, and Bakke (2006) found that 16 percent had one tumor, 1.6 percent had two tumors, and 0.2 percent had another three primary malignancies. In general, tumors occurred as metachronous tumors at 46.7 per cent. The second most common malignancy was prostate cancer. Eight cases of breast cancer were identified all in females as a second tumor. No breast cancer in men has been found. A combined risk of second primary malignancy was found to be as high as 26.6 percent in males with RCC. The study concluded that RCC patients have a substantially higher risk of developing other primary malignancies subsequently.

In another study, the effect of second primary cancers (SPCs) on RCC patients' survival has been investigated for a cohort of 3795 patients of SPCs were registered in the Surveillance Epidemiology and End Results (SEER) database between 1973 and 2006. One of the results of this study showed that these 3,795 cases were MPM and Ninety percent of all second malignancies in RCC patients were solid tumors [15,16].

A study analyzing (SEER) Program 2007 database showed that if initial primary is in the breast, the percentage of patients expected to develop multiple primaries is 10% [17] in contrast to our case which is the breast cancer was the second one.

Up to our knowledge there is no research study has been done about multiple primary malignancy in the middle region of Libya. So, the incidence is unknown and this is the first case report involving metachronous primary renal and breast malignancy.

Conclusion

In cancer patients, any suspicious lesion not responding to treatment, in contrast to other areas of the disease, should be biopsied as the presence of a another primary malignancy is always possible. Persistent anemia in cancer patients under treatment not responding to dose modifications should be further investigated as we might find a reversible underlying cause. Further investigations should be conducted to identify adverse effect of anti-angiogenesis on cancer stem cells. The interval between the first and second primaries can function as prognostic factor in patients with Multiple Primary Cancers, and therefore prolonged follow up of cancer patients is advised to detect metastatic or novel lesions. The world of research studies need to do more focus about this medical condition to avoidance any comorbid particularly.

International Journal of Stem Cells and Regenerative Medicine