|Year : 2022 | Volume
| Issue : 2 | Page : 66-69
An ordeal of multiple pathologies in a 45-year-old homemaker in a developing country: Synchronous cervical and breast cancer
Hadiza Theyra-Enias1, Sam Kwis2, Jummai Desiree Jimeta-Tuko3
1 Department of Radiology, Oncology Unit, Barau Dikko Teaching Hospital, Kaduna, Kaduna State, Nigeria
2 Department of Radiology, Oncology Unit, Jos University Teaching Hospital, Jos, Nigeria
3 Department of Radiology, Federal Medical Centre, Radiation and Oncology Unit, Birnin-Kebbi, Kebbi State, Nigeria
|Date of Submission||03-May-2021|
|Date of Decision||04-Mar-2022|
|Date of Acceptance||21-Jun-2022|
|Date of Web Publication||17-Dec-2022|
Department of Radiology, Oncology Unit, Barau Dikko Teaching Hospital, P.O. Box 9727, Lafiya Road, Kaduna, Kaduna State
Source of Support: None, Conflict of Interest: None
Globally, breast cancer is the most frequently diagnosed cancer in females and a leading cause of cancer death. On the other hand, cervical cancer is the fourth most common cancer among females worldwide. In the less developed countries, it is the second most diagnosed cancer and third leading cause of cancer death in women. Synchronous malignancy of the breast and cervix is rare due to different etiological factors. Comorbidities such as hypertension and diabetes are frequent findings in patients with cancer. In a study in this environment, diabetes mellitus was the second most common comorbidity in the elderly cancer patients. This is the case report of a 45-year-old homemaker with cervical cancer and incidental finding of a synchronous breast cancer.
Keywords: Breast cancer, cervical cancer, diabetes mellitus, Nigeria, synchronous
|How to cite this article:|
Theyra-Enias H, Kwis S, Jimeta-Tuko JD. An ordeal of multiple pathologies in a 45-year-old homemaker in a developing country: Synchronous cervical and breast cancer. J Radiat Med Trop 2022;3:66-9
|How to cite this URL:|
Theyra-Enias H, Kwis S, Jimeta-Tuko JD. An ordeal of multiple pathologies in a 45-year-old homemaker in a developing country: Synchronous cervical and breast cancer. J Radiat Med Trop [serial online] 2022 [cited 2023 Jun 3];3:66-9. Available from: http://www.jrmt.org/text.asp?2022/3/2/66/364182
| Introduction|| |
Multiple primary cancers are usually defined as de novo malignant tumors of different histological origins in one person.
The first case of multiple primary cancers in a patient was reported by Billroth over 100 years' ago. Over the years, there has been an increase in such occurrence partly due to the increase in life expectancy of cancer survivors, advancements in treatment, and comprehensive screening protocols used in cancer patients. The malignancies may occur at the same time or follow each other after a period of time. Reported cases of synchronous tumors have mainly been described in the respiratory, gastrointestinal, and genitourinary systems. Synchronous gynecological malignancies are occasionally observed, and the most reported combination is endometrial-ovarian neoplasms. In elderly males, prostate cancer has been reported as a common incidental autopsy finding in patients with multiple primary cancers. Comorbidity is common among cancer patients and plays a major role in the treatment and outcomes of people with cancer. Epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer. Type 2 diabetes and cancer share many risk factors, but potential biologic links between the two diseases are incompletely understood.
| Case Report|| |
A 45-year-old homemaker presented with a 6-month history of postcoital and inter-menstrual bleeding which was initially associated with blood clots and occasionally described as spotting. Bleeding episodes said to last between 3 and 7 days with bleeding-free interval of 2 weeks. There was a history of occasional dizziness necessitating ingestion of hematinics. She also had a 4-month history of foul-smelling vaginal discharge. No contributory gastrointestinal or genitourinary symptoms was noted. There was a history of multiple sexual partners in the patient and most recent spouse.
She is a known diabetic diagnosed 5 years prior to presentation, which was well controlled and presently on 500 mg metformin twice daily. She is not a known hypertensive or retroviral disease patient.
She is Para1+0, nonalive. Age at first pregnancy was 15 years; she had no history of use of oral contraceptive pills or hormone replacement therapy. There was no family history of breast cancer. Index case had poor practice of breast self-examination with no prior history of clinical breast examination or mammography.
Her general condition was stable with a Karnofsky performance status of 90%. On examination, a breast mass in the upper outer quadrant of the right breast measuring 12 cm × 10 cm was palpated. It was firm, nontender and mobile with no change in skin color. There was a palpable ipsilateral nontender axillary lymph node, matted, fixed, measuring 3 cm × 4 cm in its widest dimension. The contralateral breast appeared normal with no palpable mass. Abdominal examination revealed a suprapubic mass about 20 weeks size which was nontender. Vaginal examination revealed a nodular mass in the cervix involving the pelvic side walls and extending to the lower third of the vagina. Digital rectal examination revealed anal tags with normal sphincteric tone and a freely mobile rectal mucosa.
Abdominopelvic ultrasound scan findings were a bulky cervical mass measuring 7.5 cm × 6.4 cm with mild hydronephrosis of the left kidney, infiltration of the bladder base and multiple uterine fibroids. Fasting blood sugar was 4.7 Mmol/L while random blood sugar was 7.8 Mmol/L before the commencement of chemotherapy. Hemogram was 12 g/dl, WBC 5 × 109/L, platelets 200,000/mm3, renal and liver function tests were all within normal limits, retroviral screening was negative. Chest X-ray was normal; mammography of the right breast was suspicious of malignancy (BIRADS 5) while the left breast revealed BIRADS 1. She had examination under anesthesia and punch biopsy of the cervical lesion showed squamous cell carcinoma of the cervix (large cell nonkeratinizing).
She was staged as Federation of Gynecology and Obstetrics IVA cancer of the cervix.
Trucut biopsy of the right breast mass confirmed invasive carcinoma of the right breast (no special type), and sample of ipsilateral axillary lymph node revealed invasive ductal carcinoma. Immunohistochemistry was to follow. Diagnosis was synchronous malignancies (advanced cancer of the cervix with locally advanced stage 3 invasive carcinoma of the right breast).
As there are no specific guidelines regarding the management of synchronous breast and cervical cancer, management decision was taken using a multidisciplinary team approach and based on the prevailing cervical cancer symptoms of vagina bleeding and discharge, with low backache and nonincreasing breast mass. Whilst waiting for immunohistochemistry result, she was scheduled to receive chemotherapy, mastectomy with lymph node dissection, ± postmastectomy radiotherapy to the chest wall and draining lymph nodes based on high-risk pathological findings after mastectomy, radiotherapy to the pelvis and brachytherapy. Therefore, she commenced combination chemotherapy based on the tumor biology of both cervical and breast cancer - I.V Cisplatin 50 mg/m2 and I.V Paclitaxel 175 mg/m2 both on day 1 every 3 weeks for 3 courses as neo-adjuvant subject to satisfactory hemogram, blood chemistries, and performance status.
She was re-evaluated after the 3rd course to assess the possibility of a mastectomy. The breast mass had reduced significantly to a present size of 6 cm × 6 cm. However, the breast surgeons insisted on completing cytotoxics before surgery. She completed six cycles with same regimen and achieved excellent response, residual breast mass was 3 cm × 4 cm. Diabetes mellitus was well controlled during chemotherapy, as fasting blood sugar was done at intervals, and she was monitored in the endocrine clinic. Chemotherapy was well tolerated throughout the six courses.
She commenced external-beam radiotherapy to the pelvis; a dose of 54Gy in 27 fractions was prescribed on the cobalt machine. However, treatment was interrupted at 42Gy in 21 fractions on account of 60Co machine break down and was referred to continue radiotherapy at a center with a functional machine. The patient returned to clinic 5 months after referral, unable to complete radiotherapy to the pelvis and have surgery to the breast due to financial constraints. She complained of copious foul-smelling vaginal discharge, and on examination, there was an increase in the size of the breast mass from 3 cm × 4 cm to 4 cm × 6 cm. She was counseled on the need to complete treatment due to tumor progression. Investigations were ordered for re-evaluation and referred to the department of social welfare for financial assistance. Patient was lost to follow-up while trying to source for funds to complete her treatment.
| Discussion|| |
Double primary malignancies could be divided into two categories depending on the interval between tumor diagnoses. Synchronous malignancies are tumors that occur either simultaneously or within 6 months after the first malignancy was diagnosed, while metachronous malignancies are secondary tumors that develop 6 months after, or even more than that from the first malignancy.
The criteria used for the diagnosis of double primary malignancies have primarily been given by Warren and Gates.
Warren and gates criteria for diagnosis of double primary malignancies (1932)
- Each tumor should present a definite picture of malignancy
- Each tumor should be histologically distinct
- Probability of one being the metastasis of the other must be excluded.
Although synchronous primary malignancies are uncommon, it is not an unusual phenomenon to have a second malignancy in a patient with a known malignant tumor. In epidemiological studies, the frequency of multiple primaries is reported to be in the range of 2%–17%.
The lesions can be limited to a single organ or may involve multiple organ systems. The second cancers not only add to the morbidity and mortality of the patients but are distressing to the treating surgeon; hence, there is a need to study the nature of these double malignancies. The pathophysiology leading to the occurrence of multiple primary malignancies has been theorized to be common aetiological factors/carcinogens in an exposed epithelial surface which is also called "field cancerization" commonly seen in head and neck tumors. Other etiological agents associated with the development of multiple tumors include persistent exposure to carcinogens, radiation and chemotherapy for the primary cancer, immunologic and genetic defects, organ transplant and the increasing use of newer treatment manipulation, targeted therapies and immunomodulators.,
In Nigeria, cancer of the breast and cervix are the most common malignancies in females but have diverse etiological factors. Women with higher socio-economic status, obese, nulliparous, low parity, late age at first pregnancy, use of hormonal therapy and history of familial cancers are more susceptible to develop breast cancer., Human papilloma virus infection on the other hand is the most common causative agent for cervical cancer and risk of disease is higher among those with low socioeconomic status, early age of coitus, multiparous women, and history of sexual promiscuity in the index case or spouse. However, the association between both malignancies occurring synchronously may be mere coincidence or due to an unknown factor.
Treatment of the condition
The goal of management when two active malignancies are diagnosed at the same time is: tumor control and improved quality of life. However, the challenge is to find a treatment strategy that is effective against both cancer types without increased toxicity or negative impact on the overall outcome. In the index case, cisplatin and paclitaxel were prescribed as neo-adjuvant chemotherapy agents bearing in mind the histological types of both malignancies and the synergistic effect of both therapies. The NCCN guidelines for breast cancer involve the use of taxanes, and for cervical cancer cisplatin is indicated in its management, this informed the use of this combination.,
The standard of care in cervical cancer stage IVA is either concurrent chemo-radiation plus brachytherapy, neo-adjuvant chemotherapy followed by surgery, radiation alone or pelvic exenteration depending on disease stage and the patient's performance status. For locally advanced breast cancer treatment involves neo-adjuvant chemotherapy, surgery, adjuvant radiotherapy, endocrine therapy, and monoclonal antibodies depending on the molecular subtype. Index case was scheduled for a mastectomy, ± post mastectomy radiotherapy to the chest wall and draining lymph nodes based on the high-risk pathological findings after mastectomy which she did not receive.
Strong evidence suggests that cancer incidence is increased in patients with diabetes mellitus due to possible presence of shared cancer promoting factors, and a lower rate of cancer screening in patients with diabetes mellitus as documented in the literature. The reasons for the lower rates of screening are not clear but seen globally as documented in the United States and Spain.,,
The risk for several types of cancer including cancers of the pancreas, liver, breast, colorectal, urinary tract, and female reproductive organs has been demonstrated to be increased in diabetic patients. Nonetheless, for cervical cancer, the mechanisms postulated for increased cancer risk in diabetics include hyperglycemia, hyperinsulinemia with stimulation of Insulin-like growth factor-1 axis, obesity, increased cytokine production, tobacco smoking and intracellular signaling pathways. For the index case, the increased risk for cervical cancer was most probably the young age at first sexual intercourse, positive history of multiple sexual partners in present spouse. For breast cancer, low parity was most probably the risk factor.
She could not complete treatment due to financial constraint. Difficulty in accessing treatment, frequent breakdown of radiotherapy machine, prolonged waiting time, health care workers strike, prevailing poverty/lack of funds to continue treatment, religious and cultural belief and the nonchalant attitude to treatment are some of the reasons why patients do not complete treatment in this environment.,
| Conclusion|| |
In conclusion, synchronous cancers although uncommon do occur. As such, patients who present with a single cancer should be thoroughly evaluated for the possibility of a second co-existing malignancy. Importance of breast awareness/self-breast examination, access to timely intervention including radiotherapy improves outcome of patients. The devastating consequences of frequent machine breakdown and lack of funds cannot be over emphasized.
The lack of a well-established patient navigation system to follow-up patients once they default or get lost to follow-up.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jena A, Patnayak R, Lakshmi AY, Manilal B, Reddy MK. Multiple primary cancers: An enigma. South Asian J Cancer 2016;5:29-32.
] [Full text]
Das S. Synchronous and metachronous cancers: An update. Ann Clin Case Rep 2017;2:1388.
Acharya P, Ramakrishna A, Kanchan T, Magazine R. Dual primary malignancy: A rare organ combination. Case Rep Pulmonol 2014;2014:760631.
Abu-Zaid A, Alsabban M, Abuzaid M, Alomar O, Salem H, Al-Badawi IA. Triple synchronous primary neoplasms of the cervix, endometrium, and ovary: A rare case report and summary of all the English PubMed-indexed literature. Case Rep Obstet Gynecol 2017;2017:9705078.
Sarfati D, Koczwara B, Jackson C. The impact of co morbidity on cancer and its treatment. CA Cancer J Clin 2016;66:337-50.
Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al.
Diabetes and cancer: A consensus report. Diabetes Care 2010;33:1674-85.
Bagri PK, Singh D, Singhal MK, Singh G, Mathur G, Jakhar SL, et al.
Double primary malignancies: A clinical & pathological analysis report from a regional cancer institute in India. Iran J Cancer Prev 2014;7:66-72.
Agrawal R. Synchronous dual malignancy: Successfully treated cases. J Cancer Res Ther 2007;3:153-6.
Vogt A, Schmid S, Heinimann K, Frick H, Herrmann C, Cerny T, et al.
Multiple primary tumours: Challenges and approaches, a review. ESMO Open 2017;2:e000172.
Joseph SC, Darlington DC, Anitha GF. A retrospective and prospective study of double malignancies in a tertiary care hospital in South India – A ten years' experience. Int Surg J 2016;3:674-82.
Thottian AG, Mallick S, Venkatesulu B, Kumar R, Haresh K, Gupta S, et al
. Surviving triple trouble: Synchronoos breast and cervical cancer, HIV infection and myocardial infarction. Breast J 2016;23:731-5.
Ray A, Mukundan H, Bahadur AK, Rautela RS, Naik SL, Sharma BK. A rare case of two malignancies: Carcinoma of the breast and uterine cervix. Indian J Clin Biochem 2000;15:60-2.
Gradishar WJ, Moran MS, Abraham J, Aft R, Agnese D, Allison KH et al.
NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Ver. 8.2021. National Comprehensive Cancer Network, Inc.; 2021.
Abu-Rustum NR, Yashar CM, Bradley K, Campos SM, Chon HS, Chu C, et al.
NCCN Clinical Practice Guidelines in Oncology. Cervical Cancer. Ver. 1.2021. National Comprehensive Cancer Network, Inc.; 2021.
Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N, et al.
Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28:iv72-83.
Klein J, Tran W, Watkins E, Vesprini D, Wright FC, Look Hong NJ, et al.
Locally advanced breast cancer treated with neoadjuvant chemotherapy and adjuvant radiotherapy: A retrospective cohort analysis. BMC Cancer 2019;19:306.
Onitilo AA, Engel JM, Glurich I, Stankowski RV, Williams GM, Doi SA. Diabetes and cancer I. Risk, survival, and implications for screening. Cancer Causes Control 2012;23:967-81.
Beckman TJ, Cuddihy RM, Scheitel SM, Naessens JM, Killian JM, Pankratz VS. Screening mammogram utilization in women with diabetes. Diabetes Care 2001;24:2049-53.
Karathanasi I, Kamposioras K, Cortinovis I, Karampoiki V, Alevizaki P, Dambrosio M, et al.
Moving ahead in diabetics' cancer screening; food for thought from the Hellenic experience. Eur J Cancer Care (Engl) 2009;18:255-63.
Jiménez-Garcia R, Hernandez-Barrera V, Carrasco-Garrido P, Gil A. Prevalence and predictors of breast and cervical cancer screening among Spanish women with diabetes. Diabetes Care 2009;32:1470-2.
Lopez-Hernandez D. Type 2 diabetes mellitus and habit lifestyle increases the risk of cervical cancer: A cross-sectional population-based study. Austin J Obstet Gynaecol 2014;1:7.
Leng J, Ntekim AI, Ibraheem A, Anakwenze CP, Golden DW, Olopade OI. Infrastructural challenges lead to delay of curative radiotherapy in Nigeria. JCO Glob Oncol 2020;6:269-76.
Ingwu JA, Idoko C, Israel CE, Maduakolam I, Madu O. Factors influencing non-adherence to chemotherapy: Perspective of Nigerian breast cancer survivors. J Nurs Pract Today 2019;6:41-8.