|Year : 2018 | Volume
| Issue : 2 | Page : 462-464
Treatment of breast cancer in a patient of Alport syndrome-induced chronic renal failure: A triumph story
Gaurang Modi, Irappa Madabhavi, Apurva Patel, Asha Anand
Department of Medical and Pediatric Oncology, Gujarat Cancer Research Institute, Gujarat, Ahmedabad, India
|Date of Web Publication||8-Mar-2018|
Dr. Irappa Madabhavi
Department of Medical and Pediatric Oncology, Gujarat Cancer Research Institute, Gujarat, Ahmedabad
Source of Support: None, Conflict of Interest: None
Alport syndrome is a hereditary disease of the glomerular basement membrane, characterized by the familial occurrence of progressive, hematuric nephropathy with sensorineural deafness. We are reporting here a young adult female, suffering from Alport syndrome with significant family history and on maintenance twice-weekly hemodialysis (HD), had been diagnosed with triple negative earlystage right-sided breast cancer. The patient was managed successfully with surgery and adjuvant chemotherapy with 3 cycles of 5-flurouracil, doxorubicin, and cyclophosphamide and 3 cycles of docetaxel. In this case, our clinical challenge was dose reduction of chemotherapeutic agents according to creatinine clearance and timing of HD in each cycle of chemotherapy. We confronted this by dose reduction of cyclophosphamide and timing of chemotherapy was at least 12 h after HD for each and every cycle. Patient is in regular follow-up in our department since 20 months without any recurrence of the disease.
Keywords: Adjuvant chemotherapy, Alport syndrome, breast cancer
|How to cite this article:|
Modi G, Madabhavi I, Patel A, Anand A. Treatment of breast cancer in a patient of Alport syndrome-induced chronic renal failure: A triumph story. J Can Res Ther 2018;14:462-4
|How to cite this URL:|
Modi G, Madabhavi I, Patel A, Anand A. Treatment of breast cancer in a patient of Alport syndrome-induced chronic renal failure: A triumph story. J Can Res Ther [serial online] 2018 [cited 2019 Dec 5];14:462-4. Available from: http://www.cancerjournal.net/text.asp?2018/14/2/462/180680
| > Introduction|| |
Alport syndrome is a hereditary disease of the glomerular basement membrane, characterized by the familial occurrence of progressive, hematuric nephropathy with sensorineural deafness. It accounts for 0.3–2.3% of all patients reaching end-stage renal disease (ESRD). The disease is genetically heterogeneous, as it is linked with mutations in one of the genes. Mode of inheritance is X-linked or autosomal pattern. The dosage of chemotherapeutic agents used in these patients with ESRD thus frequently requires dosage reduction to avoid severe toxicities. An extensive review of the literature did not reveal a single case of management of carcinoma of breast in an Alport syndrome patient.
| > Case Report|| |
A 35-year-old female patient was diagnosed as Alport syndrome since 18 months. The diagnosis of Alport syndrome was made by significant family history and characteristic clinical findings (sensorineural deafness and anterior lenticonus) in patient and family members. She had chronic renal failure (CRF) for which she was on twice weekly maintenance hemodialysis (HD). She was waiting for a cadaveric donor for renal transplantation. She has two younger brother both had Alport syndrome. One brother's age is 32 years and underwent renal transplantation in 2002. Second brother was expired in 2012 at the age of 27 years (3 years after renal transplantation) due to acute respiratory distress syndrome. No history of consanguineous marriage in family was found. Her paternal uncle also had CRF and underwent renal transplantation.
She felt right-sided breast lump, and subsequent biopsy revealed intraductal carcinoma (IDC). Patient underwent modified radical mastectomy (MRM) by oncosurgeon. The TNM staging post MRM was pT2N0M0. Estrogen receptor, progesterone receptor, Her2 neu receptor was negative (triple negative), and histopathological examination showed Grade III, IDC, not otherwise specified type with margins were free and no lymphovascular invasion. She was referred to our medical oncology department for adjuvant chemotherapy. Her baseline hemoglobin was 10.5 gm/dl, serum creatinine was 5.2 mg/dl, and blood urea nitrogen was 45 mg/dl. She had stage V ESRD, and creatinine clearance (Cr Cl) was 12 ml/min. Other routine reports were normal. The cardiac evaluation by 2D echo showed left ventricular type of hypertrophy and ejection fraction was 55%.
She has well built with body surface area (BSA) was 1.6/m2, and she was on medication for ESRD prescribed by nephrologists. She was planned to give three cycles of 5-flurouracil, doxorubicin (adriamycin), and cyclophosphamide (FAC) and three cycles of docetaxel (80 mg/m2 per cycle), each of 21 days duration as adjuvant treatment. The doses of 5-flurouracil, doxorubicin and cyclophosphamide were 500 mg/m2, 50 mg/m2, and 500 mg/m2 per one cycle, respectively. She had A-V fistula in left forearm for dialysis, hence to administer chemotherapy; port was put by surgical procedure.
The nephrologist's opinion was taken before starting chemotherapy. The dose of cyclophosphamide was reduced to 50% in each cycle. Before starting each cycle of FAC, fresh BSA and Cr Cl was calculated. No dose modification of doxorubicin, 5-flurouracil, docetaxel was done. Close monitoring was done to avoid dehydration, excessive vomiting, anemia, fluid overload. The timing of chemotherapy was at least 12 h after dialysis. She had tolerated chemotherapy fairly, and no toxicity issue was noted. She is in regular follow-up since 20 months without any recurrence of the disease.
| > Discussion|| |
Alport syndrome is a clinically and genetically heterogeneous nephropathy. It is a progressive inherited glomerulonephritis often associated with deafness and/or ocular lesions. The majority of cases are transmitted as an X-linked semi-dominant condition occurred due to COL4A5 mutations. In this form, males are more severely affected than females. Less than 10% of cases are autosomal recessive due to mutation in either COL4A3 or COL4A4. In this rarer form, both males and females are severely affected. Alport syndrome accounts for 1–2% of all patients who start renal replacement therapy in Europe, with an estimated gene frequency of about 1 in 5000.,
The total deaths due to cancer are approximately 12%, thus ranking third after cardiovascular (52%) and infectious diseases (25%). Furthermore, the survival rate of ESRD patients suffered from malignancy is worse compared with that of ESRD cancer patients without cancer. One million people worldwide are undergone from chronic dialysis, with an increased rate in Western countries of 5% yearly. Owing to increased incidence of cancer in dialyzed patients, the management of these patients is challenging for oncologists/nephrologists. The number of patients under dialysis is increased due to aging and increasing the prevalence of Type II diabetes, a condition that is frequently associated with the deterioration of renal function.
The dosage of chemotherapeutic agents used in patients suffering from ESRD frequently requires dosage reduction to avoid severe toxicities. Furthermore, using potentially nephrotoxic anticancer drugs also will require specific monitoring and when available, specific prevention methods to help in reducing the risk for renal toxicity, especially in patients who already have abnormal renal function.,
The relationship between CRF and malignancy is multifarious. The increased incidence of cancer in ESRD patients may be explained through multiple mechanisms. Renal failure in the cancer patient is often multifactorial, but it is still clinically useful to consider causes as prerenal, intrinsic, and postrenal. Once diagnosed, cancer in a dialysis patient is generally treated as in the nondialysis patient with appropriate consideration of the renal clearance, dosing, and dialyzability of chemotherapeutic agents. Communication and co-operation among the dialysis and oncology teams is vital.
Breast cancer is the most common cancer in females of the developed countries, whereas the cervical cancer is in the developing countries. Commonly using chemotherapy in neoadjuvant and adjuvant setting in breast cancer patients are anthracycline- and taxane-based chemotherapy. Our patient was diagnosed as an Alport syndrome since childhood and was on regular HD for her ESRD. She was found to have early breast cancer and managed successfully with surgery, followed by adjuvant chemotherapy.
| > Conclusion|| |
Managing the cancer patients suffering from ESRD requires combined approach from both Oncologist and Nephrologists. Patient can be given an optimum dose of chemotherapy, with proper monitoring of the hydration and other supportive care with dose modification according to Cr Cl.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Heidet L, Gubler MC. The renal lesions of Alport syndrome. J Am Soc Nephrol 2009;20:1210-5.
Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N
Engl J Med 2003;348:2543-56.
Kashtan CE, Michael AF. Alport syndrome. Kidney Int 1996;50:1445-63.
Alport AC. Hereditary familial congenital haemorrhagic nephritis. Br Med J 1927;1:504-6.
Uchida K, Shoda J, Sugahara S, Ikeda N, Kobayashi K, Kanno Y, et al.
Comparison and survival of patients receiving hemodialysis and peritoneal dialysis in a single center. Adv Perit Dial 2007;23:144-9.
Lichtman SM, Wildiers H, Launay-Vacher V, Steer C, Chatelut E, Aapro M. International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency. Eur J Cancer 2007;43:14-34.
Launay-Vacher V, Oudard S, Janus N, Gligorov J, Pourrat X, Rixe O, et al.
Prevalence of renal insufficiency in cancer patients and implications for anticancer drug management: The renal insufficiency and anticancer medications (IRMA) study. Cancer 2007;110:1376-84.