Breast cancer in a woman with HIV/AIDS: case report and review of literature.

INTRODUCTION

Breast cancer is the most common cause of female cancer in the United Kingdom [1]. With highly active antiretroviral therapy (HAART) becoming more effective, more women with HIV are going to survive into the years where they are at increased risk of breast cancer. There have been few case reports of breast cancer in HIV-positive individuals; the first case was reported in 1988 [2] and the largest was a case series of five patients from the Cancer Control Centre in Harlem [3]. Managing therapy in patients is complicated by the risk of drug interactions and potential immune and haematological toxicity. Our experience of breast cancer in a woman with HIV infection is described below.

CASE REPORT

A 40-year-old Zimbabwean female with breast cancer and HIV was admitted to hospital with malaise, sore throat and low-grade pyrexia. A first cycle of full-dose docetaxel had been administered 4 days previously.

On examination she was haemodynamically stable with extensive oral candidiasis. No other source of infection was found. The following day her neutrophil count decreased and Filgrastim and broad spectrum antimicrobial therapy (tazocin, gentamicin, valciclovir and voroconazole) was commenced. The HIV team recommended prophylactic co-trimoxazole and erythromycin. The patient continued on HAART (ritonavir, Truvada, atazanavir). The viral load was undetectable and the CD4 count measured 103 cells/[mm.sup.3] (25.6%).

Her past medical history included a left-sided grade III intraductal carcinoma of the breast for which she had a wide local excision and axillary clearance followed by 5-fluorouracil, epirubicin, cyclophosphamide (FEC) chemotherapy and radiotherapy. Three out of 20 lymph nodes were involved. The histology revealed the tumour to be oestrogen, progesterone, and human epidermal growth factor-2 (ER/PgR/HER-2) receptor negative. During initial chemotherapy she was admitted with neutropenic sepsis and her lymphopenia prompted a review of her HIV status at that time. Following treatment of her breast cancer she was managed on multiple regimens of HAART therapy but had no HIV-related admissions to hospital. Her nadir CD4 cell count remained between 200 and 300 cells/[mm.sup.3]. Four years after presentation the patient developed recurrence of her breast cancer with pulmonary metastases for which three cycles of capecitabine were given. Re-staging CT demonstrated progression of disease and full-dose docetaxel was commenced. The viral load had been undetectable for several months.

The admission was complicated by the development of diarrhoea (Clostridium difficile-negative) with persistent pyrexia and neutropenia. Despite continued intravenous fluids she became hypotensive and confused requiring blood transfusion. On day 8, the patient developed severe mucositis and desquamation of her face, hands, soles of feet and perianal area. The following day, septic shock developed with acute renal failure, hypotension, thrombocytopenia and haematuria. After discussion with family, active medical care was withdrawn and she died the following day.

DISCUSSION

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 [4]. However, this trend does not seem to be demonstrated with respect to breast cancer [5].

A statistically significant decrease in the incidence of breast cancer was recorded following the AIDS epidemic in Tanzania [6]. Other studies have shown evidence of a reduced relative risk of breast cancer occurring in patients with HIV infection although the overall risk is unchanged [5], where relative risk is equal to the observed cancer cases divided by the expected number of cases based on contemporaneous population-based incidence rates. Furthermore, a Nordic study found a diminished incidence of breast cancer relative to other malignancies in immunosuppressed transplant recipients leading to the hypothesis that the physiological immune response is a facilitating factor in breast carcinogenesis and immunosuppression does not aid the growth of sporadic breast carcinoma [7].

The redistribution of the incidence of breast cancer in female patients with HIV/AIDS may be confounded by heightened medical surveillance at the time of diagnosis of HIV. In fact, the same report that demonstrated a decreased incidence of breast cancer in HIV-infected women, showed an increase of almost four-fold in non-homosexual male intravenous drug users [5]. This implies that the diminished relative risk is not solely due to immunosuppression by HIV offering protection against developing breast cancer. The aetiology of the increased incidence in men remains unknown.

It has also been proposed that the natural history of breast cancer is more aggressive in HIV-infected patients in America [8] although this could be explained by economic and racial disparities between patients with positive and negative HIV status. Easy access to early detection and treatment may influence survival outcome and this is highlighted in the review by Soji et al. They concluded that breast cancer survival outcome in HIV-positive patients is similar to that seen in HIV-negative women secondary to improved immune function due to HAART and if there is easy access to cancer screening [3].

Recent pre-clinical trials indicate that ritonavir, a protease inhibitor, inhibits breast cancer growth both in vitro and in vivo. Tumour regrowth between chemotherapy cycles may limit the control of recurrent/metastatic cancer and thus ritonavir could potentially arrest tumour growth. The authors suggest potential translation of its use to clinical trials [9]. In breast cancer patients already on protease inhibitors this finding may provide another explanation for the decreased relative risk. Some studies suggest that lipodystrophy caused by HAART is influenced by increased endogenous oestrogen production, oestrogen being an independent risk factor for breast cancer [10].

Not only may HIV status affect the natural history and diagnosis of breast cancer but it may also have other important effects with respect to management of the cancer. In case reports documented by El-Rayes et al. [11] three patients developed grade 4 neutropenia and one grade 3 neutropenia whilst on different chemotherapy regimens. Two patients also developed infection, which is similar to the experience in our patient. This is in keeping with results of other studies in which the incidence of myelosuppression with chemotherapy is higher in HIV-infected patients. This may be due to suppression of bone marrow function by both the HAART and chemotherapy drugs as well the destructive effects of the virus itself.

A review of 38 patients with HIV and breast cancer treated at the University of Miami Jackson Memorial Hospital with variable CD4 cell counts was presented recently at the 25th Annual Miami Breast Cancer Conference [12]. The median survival was 4.3 years, 20% died of HIV and 28% of breast cancer. In women with stage 4 disease, all died of breast cancer and those with carcinoma in situ all died as a consequence of HIV. Patients tolerated chemotherapy poorly and in two patients there was acceleration of HIV disease to AIDS with death after completing chemotherapy. There were multiple cases of shingles and one patient developed erosive Candida oesophagitis. There was an overall decrease in performance status during therapy. If chemotherapy is to be used, the authors suggested that growth factor support should be given liberally with prophylactic acyclovir and co-trimoxazole on alternative days, steroids and dose-dense therapy should be avoided and the least myelotoxic regimen (i.e. weekly therapy) used.

Our review of the literature reveals that the overall incidence of breast cancer is not increased in HIV-infected women, contrasting with some other malignancies. Much of the research appears to draw different conclusions and this may reflect the time period over which the papers have been written and the evolving nature of the treatment of HIV and breast cancer. Further case reports drawn from clinical experience will be useful in demonstrating how the two clinical entities interact.

REFERENCES

[1.] Cancer Research UK http://info.cancerresearchuk.org/cancerstats/incidence/?a=5441 (Last accessed 25th July 2007.)

[2.] Lake-Lewin D, Arkel YS. Spectrum of malignancies in HIV positive individuals. Proc Am Soc Clin Oncol, 1987, 7, 5 (Abstr.)

[3.] Soji FO, Ayoola OA, Zahra S, Hector AD. Breast cancer in women with HIV/AIDS: report of five cases with a review of the literature. J Surg Oncol, 2005, 89, 23-57.

[4.] Chiao EY, Krown SE. Update on non-acquired immunodeficiency syndrome defining malignancies. Curr Opin Oncol, 2003, 15, 389-397.

[5.] Frisch M, Biggar RJ, Engels EA, Goedert JJ. Association of cancer with AIDS-related immunosuppression in adults. J Am Med Assoc, 2001, 285, 1736-1745.

[6.] 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, 2000, 92, 301-305.

[7.] Stewart T, Tsai SC, Grayson H et al. Incidence of de novo breast cancer in women chronically immunosuppressed after organ transplantation. Lancet, 1995, 346, 796-798.

[8.] 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.

[9.] Srirangam A, Mitra R, Wang M et al. Effects of HIV protease inhibitor ritonavir on Akt-regulated cell proliferation in breast cancer. Clin Cancer Res, 2006, 12, 1883-1896.

[10.] Agurs-Collins T, Kim KS, Dunston GM et al. Plasma lipid alterations in African-American women with breast cancer. J Cancer Res Clin Oncol, 1998, 124, 186-190.

[11.] El-Rayes BF, Barenji K, Schuman P, Philip PA. Breast cancer in women with human immunodeficiency virus infection: implications for diagnosis and therapy: five case reports and a review of literature. Breast Cancer Res Treat, 2002, 76, 111-116.

[12.] http://www.cancerconf.com/media/22112/index.htm (Last accessed 25th July 2007.)

Correspondence to: Dr Subali Nallamala, Medical Oncology, Charing Cross Hospital, Fulham Palace Road, London W12 OHS, UK. Email: [e-mail]