Breast Cancer in the Setting of HIV
Identifieur interne : 000E13 ( Pmc/Corpus ); précédent : 000E12; suivant : 000E14Breast Cancer in the Setting of HIV
Auteurs : Mitul Palan ; Sami Shousha ; Jonathan Krell ; Justin StebbingSource :
- Pathology Research International [ 2090-8091 ] ; 2011.
Abstract
Oncogenesis in immunocompromised patients occurs due to a number of factors including reduced immune surveillance or other viral pathogens. Breast cancer, unlike other non-AIDS-defining cancers, does not appear associated and has rarely been reported. We describe a case with evidence of immune reactivity around the tumor, but not in the tumor itself.
Url:
DOI: 10.4061/2011/925712
PubMed: 21660281
PubMed Central: 3108579
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PMC:3108579Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Breast Cancer in the Setting of HIV</title><author><name sortKey="Palan, Mitul" sort="Palan, Mitul" uniqKey="Palan M" first="Mitul" last="Palan">Mitul Palan</name><affiliation><nlm:aff id="I1">Department of Medical Oncology, The Hammersmith Hospitals NHS Trust, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</nlm:aff></affiliation></author><author><name sortKey="Shousha, Sami" sort="Shousha, Sami" uniqKey="Shousha S" first="Sami" last="Shousha">Sami Shousha</name><affiliation><nlm:aff id="I2">Department of Histopathology, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</nlm:aff></affiliation></author><author><name sortKey="Krell, Jonathan" sort="Krell, Jonathan" uniqKey="Krell J" first="Jonathan" last="Krell">Jonathan Krell</name><affiliation><nlm:aff id="I1">Department of Medical Oncology, The Hammersmith Hospitals NHS Trust, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</nlm:aff></affiliation></author><author><name sortKey="Stebbing, Justin" sort="Stebbing, Justin" uniqKey="Stebbing J" first="Justin" last="Stebbing">Justin Stebbing</name><affiliation><nlm:aff id="I1">Department of Medical Oncology, The Hammersmith Hospitals NHS Trust, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21660281</idno><idno type="pmc">3108579</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108579</idno><idno type="RBID">PMC:3108579</idno><idno type="doi">10.4061/2011/925712</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000E13</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E13</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Breast Cancer in the Setting of HIV</title><author><name sortKey="Palan, Mitul" sort="Palan, Mitul" uniqKey="Palan M" first="Mitul" last="Palan">Mitul Palan</name><affiliation><nlm:aff id="I1">Department of Medical Oncology, The Hammersmith Hospitals NHS Trust, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</nlm:aff></affiliation></author><author><name sortKey="Shousha, Sami" sort="Shousha, Sami" uniqKey="Shousha S" first="Sami" last="Shousha">Sami Shousha</name><affiliation><nlm:aff id="I2">Department of Histopathology, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</nlm:aff></affiliation></author><author><name sortKey="Krell, Jonathan" sort="Krell, Jonathan" uniqKey="Krell J" first="Jonathan" last="Krell">Jonathan Krell</name><affiliation><nlm:aff id="I1">Department of Medical Oncology, The Hammersmith Hospitals NHS Trust, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</nlm:aff></affiliation></author><author><name sortKey="Stebbing, Justin" sort="Stebbing, Justin" uniqKey="Stebbing J" first="Justin" last="Stebbing">Justin Stebbing</name><affiliation><nlm:aff id="I1">Department of Medical Oncology, The Hammersmith Hospitals NHS Trust, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</nlm:aff></affiliation></author></analytic><series><title level="j">Pathology Research International</title><idno type="ISSN">2090-8091</idno><idno type="eISSN">2042-003X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Oncogenesis in immunocompromised patients occurs due to a number of factors including reduced immune surveillance or other viral pathogens. Breast cancer, unlike other non-AIDS-defining cancers, does not appear associated and has rarely been reported. We describe a case with evidence of immune reactivity around the tumor, but not in the tumor itself.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Oluwole, Sf" uniqKey="Oluwole S">SF Oluwole</name></author><author><name sortKey="Ali, Ao" uniqKey="Ali A">AO Ali</name></author><author><name sortKey="Shafaee, Z" uniqKey="Shafaee Z">Z Shafaee</name></author><author><name sortKey="Depaz, Ha" uniqKey="Depaz H">HA Depaz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pantanowitz, L" uniqKey="Pantanowitz L">L Pantanowitz</name></author><author><name sortKey="Connolly, Jl" uniqKey="Connolly J">JL Connolly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amir, H" uniqKey="Amir H">H Amir</name></author><author><name sortKey="Kaaya, Ee" uniqKey="Kaaya E">EE Kaaya</name></author><author><name sortKey="Kwesigabo, G" uniqKey="Kwesigabo G">G 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Patholog Res Int</journal-id><journal-id journal-id-type="iso-abbrev">Patholog Res Int</journal-id><journal-id journal-id-type="publisher-id">PRI</journal-id><journal-title-group><journal-title>Pathology Research International</journal-title></journal-title-group><issn pub-type="ppub">2090-8091</issn><issn pub-type="epub">2042-003X</issn><publisher><publisher-name>SAGE-Hindawi Access to Research</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21660281</article-id><article-id pub-id-type="pmc">3108579</article-id><article-id pub-id-type="doi">10.4061/2011/925712</article-id><article-categories><subj-group subj-group-type="heading"><subject>Case Report</subject></subj-group></article-categories><title-group><article-title>Breast Cancer in the Setting of HIV</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Palan</surname><given-names>Mitul</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Shousha</surname><given-names>Sami</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>krell</surname><given-names>Jonathan</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stebbing</surname><given-names>Justin</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor2">*</xref></contrib></contrib-group><aff id="I1"><sup>1</sup>Department of Medical Oncology, The Hammersmith Hospitals NHS Trust, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</aff><aff id="I2"><sup>2</sup>Department of Histopathology, and Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK</aff><author-notes><corresp id="cor1">*Mitul Palan: <email>mitul.palan06@imperial.ac.uk</email> and </corresp><corresp id="cor2">*Justin Stebbing: <email>j.stebbing@imperial.ac.uk</email></corresp><fn fn-type="other"><p>Academic Editor: Liron Pantanowitz</p></fn></author-notes><pub-date pub-type="collection"><year>2011</year></pub-date><pub-date pub-type="epub"><day>25</day><month>5</month><year>2011</year></pub-date><volume>2011</volume><elocation-id>925712</elocation-id><history><date date-type="received"><day>29</day><month>11</month><year>2010</year></date><date date-type="rev-recd"><day>5</day><month>4</month><year>2011</year></date><date date-type="accepted"><day>5</day><month>4</month><year>2011</year></date></history><permissions><copyright-statement>Copyright © 2011 Mitul Palan et al.</copyright-statement><copyright-year>2011</copyright-year><license xlink:href="https://creativecommons.org/licenses/by/3.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Oncogenesis in immunocompromised patients occurs due to a number of factors including reduced immune surveillance or other viral pathogens. Breast cancer, unlike other non-AIDS-defining cancers, does not appear associated and has rarely been reported. We describe a case with evidence of immune reactivity around the tumor, but not in the tumor itself.</p></abstract></article-meta></front><body><sec id="sec1"><title>1. Introduction</title><p>Very few cases of breast cancer in HIV-infected women are recorded in the literature; approximately 46 HIV-infected women to this date have been recorded. According to the World Health Organization, approximately 33.4 million people (adults and children) in the world were living with HIV in 2008, the majority of which resided in sub-Saharan Africa [<xref rid="B1" ref-type="bibr">1</xref>]. A very wide range of cancers have been associated with an increased incidence in people living with HIV [<xref rid="B2" ref-type="bibr">2</xref>, <xref rid="B3" ref-type="bibr">3</xref>]. As well as neoplasms such as Kaposi's sarcoma [<xref rid="B4" ref-type="bibr">4</xref>] and Non-Hodgkin's lymphoma [<xref rid="B5" ref-type="bibr">5</xref>], a focus of recent research has been the non-AIDS-defining cancers, that is, tumors other than Kaposi sarcoma, non-Hodgkin lymphoma, and cancer of the uterine cervix, in the setting of HIV. However, of the non-AIDS-defined cancers, breast cancer does not seem to increase in incidence within the HIV-infected population. This relationship between the two diseases has been noted worldwide, but few explanations have been forwarded as to the exact causative/noncausative relationship that the two may partake in. </p><p>This paper looks to evaluate the relationship between the HIV and breast cancer, and we propose some theories as to why HIV infection may actually protect against breast tumor development.</p></sec><sec id="sec2"><title>2. Case Vignette</title><p>A 44-year-old HIV-positive lady presented with a right breast mass in the upper outer quadrant and was diagnosed with a triple negative (i.e., oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) negative), grade 3 invasive ductal carcinoma (IDC), 15 mm × 15 mm in size, with zero out of 3 sentinel nodes involved.</p><p>She initially noticed a lump in her right breast, alongside skin and shape changes in the breast and nipple discharge. There was no history of oral contraceptive use, nor any family history of breast/ovarian cancer. Her CD4 count measured 450 cells/mm<sup>3</sup> with an HIV-1 viral load of approximately 500 copies/mL. Mammography, ultrasound, and core biopsy of the right breast confirmed the presence of the tumor. Figures of her breast pathology may be seen below (Figures <xref ref-type="fig" rid="fig1">1</xref> and <xref ref-type="fig" rid="fig2">2</xref>). CD4 and CD8 lymphocyte staining of the tissue sample showed significant lymphocytic infiltration adjacent to the tumor (but not within it).</p><p>The patient's treatment included a wide local excision of the lump with right axillary sentinel lymph node biopsy. The patient underwent 6 cycles of FEC75 chemotherapy requiring substantial dose reductions and G-CSF support, while remaining concurrently on HAART. A bone scan and a CT showed no sign of distant metastases. At the time of submission, she is completing her chemotherapy.</p></sec><sec id="sec3"><title>3. Discussion</title><p>While a number of neoplasms are well associated with HIV infection [<xref rid="B4" ref-type="bibr">4</xref>–<xref rid="B7" ref-type="bibr">7</xref>], non-AIDS-defining tumors [<xref rid="B8" ref-type="bibr">8</xref>] have more complex affiliations to HIV—some seem to also increase in incidence with infection, for example, lung cancer, myeloma, anal cancers [<xref rid="B7" ref-type="bibr">7</xref>, <xref rid="B9" ref-type="bibr">9</xref>], while it is still debated whether others (e.g., breast cancer, head and neck cancer [<xref rid="B10" ref-type="bibr">10</xref>]) have an increased incidence due to HIV.</p><p>Few studies have delved into explaining the link between HIV and breast cancer. This is not particularly surprising however, as only 48 cases of breast cancer have been noted in HIV-positive people to date [<xref rid="B11" ref-type="bibr">11</xref>]. This number may be contested due to lack of case presentation (e.g., poorer socioeconomic groups/people of the third world less likely to seek medical care) or that women with HIV may have a reduced lifespan (and therefore are less likely to reach an age at which breast cancer may occur) [<xref rid="B12" ref-type="bibr">12</xref>]. A study in 1,416 HIV-positive Thai women, with an average age of 40.8 years over 5 years, found breast cancer to be the most prominent (9.5%) non-AIDS-defining tumors (42 cases of non-AIDS tumors overall) occurring [<xref rid="B13" ref-type="bibr">13</xref>]. It is important however to note though that the number of patients with breast cancer amounted to 4: approximately 0.28% of the percentage of women, a figure not too dissimilar to what one would expect in a female cohort such as this.</p><p>The majority of studies have found no difference in the incidence of breast cancer in HIV-positive women and the HIV-negative population [<xref rid="B11" ref-type="bibr">11</xref>]. An American study by Frisch et al. found the relative risk of developing breast cancer after HIV infection was 1.1, that is, HIV infection had little impact on breast cancer incidence [<xref rid="B7" ref-type="bibr">7</xref>], and other studies have supported this [<xref rid="B9" ref-type="bibr">9</xref>, <xref rid="B14" ref-type="bibr">14</xref>]. In a sub-Saharan Tanzanian population, there was a small, yet statistically significant decrease in breast cancer incidence in the post-AIDS epidemic period (1983–1996), compared to the pre-AIDS period (1968–1983) [<xref rid="B4" ref-type="bibr">4</xref>]. Data from Rwanda additionally shows a low number of breast cancer cases despite a high HIV prevalence [<xref rid="B15" ref-type="bibr">15</xref>]. Reviews concur with these findings. For example, in South Africa, no trend has been observed [<xref rid="B16" ref-type="bibr">16</xref>].</p><p>People with HIV may develop cancer due to impaired immune surveillance, dysregulation of growth factors or cytokines, or imbalance between proliferation and differentiation [<xref rid="B17" ref-type="bibr">17</xref>]. As can be observed in our case, and in a number of other reported cases [<xref rid="B18" ref-type="bibr">18</xref>], the pathology of HIV-positive breast cancer patients is in stark contrast to noninfected women in the population. A reduction in immune function could be a reason why breast cancer prevalence remains low in patients with HIV [<xref rid="B7" ref-type="bibr">7</xref>, <xref rid="B19" ref-type="bibr">19</xref>]. Pantanowitz investigated the pathology of HIV-positive breast cancer cases, finding that the immune response to these neoplasms was considerably less compared to that found in breast cancer in nonaffected women [<xref rid="B3" ref-type="bibr">3</xref>]. Immunosuppression is a large factor in the pathogenesis of many AIDS-related cancers [<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B20" ref-type="bibr">20</xref>, <xref rid="B21" ref-type="bibr">21</xref>]. HPV, associated with anal and cervical cancer (particularly in the immunocompromised), may induce oncogenesis by altering cell-cycle control—either deactivating tumor-suppressor genes or up regulating certain oncogenes [<xref rid="B22" ref-type="bibr">22</xref>]. There is continued debate whether HIV itself may cause dysregulation of cell proliferation by insertion of provirus nuclear material near/within human oncogenes [<xref rid="B20" ref-type="bibr">20</xref>].</p><p>The prognostic significance of stromal lymphocytic infiltration in breast cancer is disputed [<xref rid="B23" ref-type="bibr">23</xref>–<xref rid="B26" ref-type="bibr">26</xref>]. Previously, it has been linked to a poor prognosis [<xref rid="B3" ref-type="bibr">3</xref>, <xref rid="B27" ref-type="bibr">27</xref>] (e.g., CD4- and CD8-T lymphocyte infiltration has been associated with high grade intraductal carcinomas [<xref rid="B18" ref-type="bibr">18</xref>]). This is not a relationship one would expect between the two as the immune system in nonimmunocompromised individuals plays a pivotal role in removing cancerous cells [<xref rid="B18" ref-type="bibr">18</xref>]. However, the control over cell proliferation here is slightly more complex. CD4- and CD8-T lymphocytes are implicated in acquired immune responses to cancer, but are tightly regulated by T regulatory cells [<xref rid="B28" ref-type="bibr">28</xref>]. Various studies have shown that T regulatory cells are found in abundance in neoplastic breast tissues, both in situ and in invasive carcinomas—their recruitment in intratumoral and peritumoral tissue may enable malignant cells to evade the host immune response, and as such may represent a marker of breast cancer progression [<xref rid="B28" ref-type="bibr">28</xref>, <xref rid="B29" ref-type="bibr">29</xref>]. This may explain the absence of intratumoral lymphocytic infiltration, as seen in our patient (Figures <xref ref-type="fig" rid="fig1">1</xref> and <xref ref-type="fig" rid="fig2">2</xref>). In HIV, however, the reduction in T cell count suggests that with a decreased number of T regulatory cells (along with some CD4- and CD8-T lymphocytes), the host is unable to restrict an immune response to cancer growth. This may indirectly benefit the patient from developing breast cancer, but perhaps not from other cancers [<xref rid="B8" ref-type="bibr">8</xref>]. Studies in posttransplant, non-HIV immunocompromised women (a similar subgroup to HIV-positive women) also support this proposition [<xref rid="B16" ref-type="bibr">16</xref>, <xref rid="B30" ref-type="bibr">30</xref>]. </p><p>HAART-induced restoration of immune function with treatment [<xref rid="B31" ref-type="bibr">31</xref>] may prevent initial breast tumorigenesis. Antiretrovirals such as ritonavir have been implicated in targeting both viral and tumorigenic proteins [<xref rid="B32" ref-type="bibr">32</xref>] that may play some part in breast cancer proliferation or tumor progression/resistance [<xref rid="B33" ref-type="bibr">33</xref>, <xref rid="B34" ref-type="bibr">34</xref>]. These drugs may decrease the availability/activity of proangiogenic factors [<xref rid="B5" ref-type="bibr">5</xref>, <xref rid="B35" ref-type="bibr">35</xref>], interfere with other oncogenic cytokine signalling pathways [<xref rid="B31" ref-type="bibr">31</xref>], or target intracellular mitogenic signalling pathways (which tumors use to proliferate [<xref rid="B36" ref-type="bibr">36</xref>, <xref rid="B37" ref-type="bibr">37</xref>]). There is also some evidence to suggest that HIV viral proteins may induce tumor cell cytotoxicity and apoptosis [<xref rid="B38" ref-type="bibr">38</xref>]. 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Nutrition</italic></source><year>2002</year><volume>76</volume><issue>6</issue><fpage>1428</fpage><lpage>1434</lpage><pub-id pub-id-type="pmid">12450913</pub-id></element-citation></ref><ref id="B40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Colecraft</surname><given-names>E</given-names></name></person-group><article-title>HIV/AIDS: nutritional implications and impact on human development</article-title><source><italic>Proceedings of the Nutrition Society</italic></source><year>2008</year><volume>67</volume><issue>1</issue><fpage>109</fpage><lpage>113</lpage><pub-id pub-id-type="pmid">18234139</pub-id></element-citation></ref><ref id="B41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Leong</surname><given-names>PP</given-names></name><name><surname>Mohammad</surname><given-names>R</given-names></name><name><surname>Ibrahim</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast</article-title><source><italic>Immunology Letters</italic></source><year>2006</year><volume>102</volume><issue>2</issue><fpage>229</fpage><lpage>236</lpage><pub-id pub-id-type="pmid">16246429</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="fig1" position="float"><label>Figure 1</label><caption><p>Low (a) and high (b) power images of our patient's invasive ductal carcinoma of the breast. Sections were stained with haematoxylin and eosin. (a) shows a large area of central tumor necrosis with a peripheral rim of viable tumor cells. (b) shows invasive tumor cells with high nuclear grade.</p></caption><graphic xlink:href="PRI2011-925712.001"></graphic></fig><fig id="fig2" position="float"><label>Figure 2</label><caption><p>CD4 (a) and CD8 (b) staining of the tumor sections. Both cell populations were found adjacent to, but not infiltrating, the tumor.</p></caption><graphic xlink:href="PRI2011-925712.002"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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