Prevalence of HIV/AIDS among Breast Cancer Patients and the associated Clinico-pathological features

Sseggwanyi J1, Galukande M1, Fualal J2, Jombwe J2 Affi liations:1-Department of Surgery, Makerere University College of Health Sciences, Kampala 2-Department of Surgery, Mulago National Referral Hospital, Kampala Correspondence author: Moses Galukande, Department of Surgery, College of Health Sciences Makerere University P.O. Box 7072 Kampala, Uganda E-mail:

 

Abstract

Introduction: There is uncertainty as to the exact interaction between HIV and Breast Cancer. Available studies are inconclusive about any relation whether causal or protective and the number of patients in these studies small.

 

Objective: To determine the prevalence of HIV among confirmed incident breast cancer cases and to describe the associated clinico-pathological features.

 

Design: Analytical cross sectional study

 

Methods: Over a period of 6 months consecutively eligible patients were recruited from the Mulago Hospital breast clinic. Breast lesions were biopsied and blood withdrawn for HIV sero-survey. Collected data was double entered into Epidata version v 3.1.1, exported to STATA 10.0 for analysis.

Results: Sixty two breast cancer patients consented to participate in the study and of these, 22(35.48%) were positive for HIV compared to HIV prevalence in the general population of 6-7%. All the participants were female. The mean age of HIV negative subjects was 45 years (range: 21-80 years) and for HIV positive subjects was 32.4 years (range 18-52 years). There was a significant association between HIV status and age, BMI and CD4 Counts as well as for histological grade and stage (P< 0.024).

 

Conclusion: The prevalence of HIV among the studied breast cancer group was significantly higher than that in the general population. HIV was associated with poor prognostic factors. A high index of suspicion of the co-existence of these two diseases in a context of high HIV preva-lence is warranted. Future studies should explore for a causal association.

 

Introduction

Global statistics demonstrate that almost one third (32%) of all cancers diagnosed in women are breast can-cer (1). In Uganda, the incidence of breast cancer has risen from 11:100,000 in the 1960s to 31:100,000 in 2006 (2). It is second to Kaposi sarcoma in cancers affecting women in the HIV/AIDS (3). The breast tumors seen in Sub Sa-haran Africa present in relatively younger women and mostly in late stage (III and IV), run an aggressive course and carry a low 5 year survival rate (56%) (4, 5) .

 

Sub-Saharan Africa still remains the region most heav-ily affected by HIV worldwide, accounting for over two thirds (67%) of all people living with HIV and for nearly three quarters (72%) of AIDS-related deaths in 2008. An estimated 1.9 million [1.6 million–2.2 million] people were newly infected with HIV in sub-Saharan Africa in 2008, bringing to 22.4 million [20.8 million–24.1 mil-lion] the number of people living with HIV (6). Non-AIDS-defining cancers that have shown increased incidence in studies of population-based registries of people with HIV/AIDS include multiple myeloma, lip cancer and lung cancer [7], but data about Breast cancer as an AIDS or Non AIDS defining cancer is limited and con-flicting (8) and the association of HIV infection with breast carcinoma is still unclear (9). The longer patient survival of HIV patients is expected to result in higher prevalence of breast cancer in these patients (10).

 

Patients with HIV and breast cancer present two distinct challenges to the clinician: to confirm the diagnosis and accurately stage breast cancer, and to evaluate the safety and timing of surgery and adjuvant treatment in the set-ting of immunosuppression (11, 12). There is no clear data about the clinicopathological cor-relation of breast cancer in HIV-positive patients and their current prevalence is not known in our setting.

 

This study was conducted to determine the prevalence of HIV in breast Ca patients and determine if the clinico-pathological features of the disease are different in HIV+ versus HIV- patients

 

Methodology

Study Design: An analytical cross sectional study Study Duration: The study was conducted over a period of six months from January 2011 to June 2011 inclusive. Study Setting: Mulago hospital is the National Referral and Teaching hospital for Makerere University in central Uganda. It has a bed capacity of about 1700. Incident cases were recorded from Mulago hospital surgical out-patient department (breast clinic) and ward 3C (in-pa-tient ward).

Study participants

All patients with histologically confirmed breast cancer who were able to give relevant information and consent to participate in the study were included.

 

The sample size (n) was calculated using the modified simple random sampling formula by Wayne [17], seek-ing to establish the prevalence of subjects. Ethical ap-proval was sought and all participants consented.

 

Laboratory Procedures

HIV diagnosis was made using a standard diagnostic method. The blood was tested once using the ELISA method which is 99.3% to 99.7% sensitive and 99.7% specific (Statpak test kit) [18]. The participants under-went pre and post HIV/AIDS screening counseling by a trained counselor.

 

Core breast biopsies, fixed in 10% formalin solution were processed for paraffin embedding for Heamatoxy-lin and Eosin staining at the Pathology Department of Mulago Hospital. The slides were reported according to Evans Histological classification and Nottingham grad-ing of tumors (19).

 

Data Collection and Analysis

Data were entered, verified and analyzed using the Epi-data and SPSS computer program. The confidence inter-val was set at 95%. The level of significance as p<0.05.

 

Results

A total of 62 participants with histological diagnoses of breast cancer were studied. Of these, 22 participants were positive for HIV (35.5%). There was a significant relationship between HIV status and the socio-demo-graphic plus clinic pathological characteristics except tribe among the 62 Breast cancer participants (Table 1).

 

Discussion

Prevalence

The study findings demonstrated a 35.5% prevalence of HIV among this group of patients with breast can-cer. This is similar to a study done 10 years earlier at the same facility that found the HIV prevalence to be 35.7% (16). Given that the HIV prevalence in the general popu-lation is 6.7% (17), a 7-fold difference in prevalence in this breast cancer patients group may suggest a link be-tween breast cancer and HIV infection even though this study wasn’t designed to confirm a causal relationship.

 

We would have anticipated a corresponding drop in prevalence of HIV among breast cancer patients since HIV in the general population has dropped over the years among the age group that tested positive (18).

 

Age

Our findings demonstrate a mean age of 32.4 years among the HIV positives. This finding also suggests that breast cancer is affecting the younger population compared to earlier studies which found the mean age for breast cancer to be 41.7years and 47 years (4, 5, 13). While breast cancer seems to be more common in age group of 30-39years, participants that had both HIV and breast cancer were mostly observed among the 18-29years group. The predominance among pre meno-pausal women begs the question whether HIV infection may indeed be a risk factor.

BMI, CD4 count and stage

The proportions of subjects with normal Body Mass In-dex (BMI) were almost equally distributed by HIV sta-tus. However high BMI was most observed among the non-reactive (83.87%). Perhaps the comorbid condi-tions that come with HIV infection are likely to have reduced the patient weights. Among the 22 reactive par-ticipants, 8 (36%) were on treatment with anti-retroviral drugs (ART). Among those who never had ART (64%), 3 (21.4%) were only prophylactic treatment as recom-mended by Ministry of Health (MoH) guidelines which state that; Cotrimoxazole prophylaxis should be given to all HIV-infected adults and children in Uganda regard-less of whether they are on antiretroviral therapy (ART) or not. The low use of prophylaxis may be explained ei-ther by the delay in HIV diagnosis or limited access to care. These subjects were however referred to HIV care centres for the prophylaxis and further treatment. Among the HIV positives, 3(13.6%) had their CD4 less than 250cells/mm3. Nineteen (86.4%) respondents and all those who were HIV negative had their CD4+ counts greater than 250cell/mm3. The finding that all negative participants had CD4+ count greater than 250cell/mm3 may be difficult to interpret and may require in-depth exploration.

 

Most of the HIV positive participants were observed to be in clinical stage III of breast cancer (47.06%) whereas those without HIV were mainly in clinical stage II of breast cancer (80.77%). One patient had stage IV dis-ease and this patient also tested positive for HIV. (P-val-ue =0.024[fisher’s exact test]) This may suggest that HIV probably accelerates the natural progression of breast cancer to advanced disease (12), and therefore a poor prognostic indicator.

 

Histopathology

Invasive ductal carcinoma (NOS) was the most common type of breast cancer observed in the study of which 12 (25.53%) were HIV positive making up 54.5% of the HIV reactive participants. This is in agreement with an earlier case series report (9). Medullary carcinoma was observed in 7 individuals of which 5 (71.4%) were re-active. Both participants who had scirrhous carcinoma were also positive with HIV. This supports the fact that breast cancer in the face of HIV presents with unusual forms (8). Histological grading of breast cancer in the setting of HIV was also significant with the majority of HIV posi-tive individuals (n=13, 50%) having high grade cancer and 9(30%) having intermediate grade disease with none of them exhibiting low grade breast cancer. Among the non-reactive participants, 13(50%) of them had high grade cancer, 21(70%) had intermediate grade and 6(100%) had low grade breast cancer. This suggests that HIV is associated with poor grades. A similar suggestion was published by El-Rayes et al, 2002 in a 5 patient case report series (12).

 

Limitations of the study

A single sample was collected and analysed once for HIV infection. The “window period” could affect the results of the true prevalence of HIV in breast cancer patients. It is possible that there could have been referral bais based on the premise that HIV positive patient health managers promptly refer their patients to further care. However a significant proportion of the patients in this study only knew of their HIV status during the study. It is also conceivable that if there was referral bias they should present at earlier stages than the HIV negative ones but this wasn’t the case.

 

Conclusions

The prevalence of HIV among breast cancer patients was higher than in the general adult population. Breast can-cer is occurring more in the younger population than observed before and seems to impact negatively on the progression of breast cancer.

 

A high index of suspicion regarding breast cancer and HIV co-existence is warranted. A further in-depth study for a causal association recommended.

 

Acknowledgments

Special gratitude to BTC, all the participants in this study and the supportive members of the Department of Sur-gery at Makerere University.

 

References

 

  1. American Cancer Society, Breast Cancer Facts and Figures 2009-2010. http://www.cancer.org/downloads/STT/F861009 final%209-08-09

  2. Parkin DM, Nambooze S, Wabwire-Mangen F, et al. Chang-ing Cancer Incidence in Kampala, Uganda, 1991-2006. Int J Cancer 2009; 126(5):1187-1195

  3. The Uganda Breast Cancer Working Group, Breast cancer guidelines for Uganda Afr Health Sci 2008; 3(1):47-50

  4. Gakwaya A, Kigula MJ, Kavuma A, et al.. Cancer of the breast: 5 – year survival in a tertiary hospital in Uganda. Br J Cancer 2008; 99(1):63-67

  5. Gondos A.B.H, Wabinga H, Parkins D.M. Cancer survival in Kampala, Uganda. Brit J of Cancer 2005; (92):1808-1812

  6. AIDS epidemic up date: November 2009. UNAIDS/09.36E / JC1700E”.

  7. Chiao EY, Krown SE. Update on non-acquired immunode-ficiency syndrome defining malignancies. Curr Opin Oncol 2003; 15: 389-397.

  8. Naeem L, Fauzia R, Troy G. Breast Cancer and HIV in the Era of HAART: A case Report and Review of the Literature. 2010; 61(3): 6-40

  9. Soji Fo, Ayoola OA, Zahara S, et al. Breast Cancer in Women With HIV/AIDS: Report of Five Cases With a Review of the Literature. Journal of Surgical Oncology 2005; 89; 23-27.

  10. Guiget M, Curie M. "Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual ma-lignancies (FDH-ANRS CO4): A prospective cohort study" Lancet Oncol 2009; DOI: 10.1016/S1470-2045(09)70282-7.

  11. Voutsadakis IA, Silverman LR. Breast cancer in HIV-positive women: a report of four cases and review of the literature. Cancer Invest 2002; 20: 452-457.

  12. El-Rayes BF, Barenji K, Schuman P, et al. Breast cancer in women with human immunodeficiency virus infection: im-plications for diagnosis and therapy: five case reports and a review of literature. Breast Cancer Res Treat. 2002; 76: 111-116.

  13. Amir H, Kaaya EE, Kwesigabo G Kiitinya JN. Breast cancer before and during the AIDS epidemic in women and men: a study of Tanzanian cancer registry data 1968 to 1996. J Natl Med Assoc. 2001; 92:301-305.

  14. Wayne D.W: Biostatics; A foundation for Analysis in Health Science: 5th edition. John Wiley and Sons; 1987. p157.

  15. David JBA. Evans Histological Appearance of Tumors. Fourth Edition 1990. 424; 441-450..

  16. Najjuka JL (SR). Is there any association between Breast Can-cer and HIV-AIDS in women in Uganda? 2000.

  17. Hladik W, Musinguzi J, Kirungi W, et al. The estimated bur-den of HIV/AIDS in Uganda, 2005-2010. AIDS Feb 2008; 22(4): 503-510.doi:10.1079/QAD. Obo 13e3282f470be