Malignancies in lupus demand clinical caution

BUENOS AIRES – Incidences of certain cancers, particularly lymphomas, have been shown to be higher in people with systemic lupus erythematosus, while hormone-influenced breast, ovarian, and endometrial cancers have recently been found to occur less often in SLE patients than in the general population.

At the 10th International Congress on SLE, the researchers responsible for these findings discussed their implications for clinical practice.

Dr. Ann Clarke of McGill University, Montreal, coauthor of a large case-cohort study that found neither immunosuppressant drug use nor disease activity correlated with lymphoma risk as hypothesized (Ann. Rheum. Dis. 2013 Jan. 8 [doi:10.1136/annrheumdis-2012-202099]), said that clinicians should nonetheless consider a history of malignancies when deciding whether to prescribe immunosuppressants.

The study by Dr. Clarke and her colleagues, led by Dr. Sasha Bernatsky of McGill, enrolled 75 SLE patients with lymphoma and 4,961 cancer-free controls with SLE, seeking to determine associations between lymphoma risk and exposures to cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarials, or steroids. The team also looked at Sjögren’s syndrome, disease duration, and disease activity as potential indicators of risk.

Although cyclophosphamide use was seen more frequently among the lymphoma cases (20%) than in the controls (16.8%), this difference did not reach statistical significance. "There isn’t a strong signal that the drugs are responsible," Dr. Clarke said, but she nonetheless argued for caution in the clinic.

"If there is a remote history of malignancy – more than 5 years, certainly more than 10 – I would proceed [with immunosuppressants]," she said. "If there is a recent history, I would try to avoid them, using rituximab or belimumab as appropriate."

Dr. Clarke’s team, again led by Dr. Bernatsky, also conducted research that examined the incidence of specific cancers in an international cohort of 16,409 patients with SLE (J. Autoimmun. 2013 Feb. 11 [doi:10.1016/j.jaut.2012.12.009]).

This study showed that lupus patients had a threefold higher risk for hematological cancers, especially non-Hodgkin’s lymphoma, and a slightly elevated risk for cancer overall, but saw fewer hormone-sensitive cancers than expected, with the standardized incidence ratio of 0.73 for breast cancers (95% confidence interval [CI], 0.61-0.88), 0.44 for endometrial cancers (95% CI, 0.23-0.77), and 0.64 for ovarian cancers (95% CI, 0.34-1.10).

"There certainly seems to be a convincing signal that female hormone-sensitive cancers appear to be decreased in patients with lupus," said Dr. Clarke, who is also codirector of the lupus clinic at Montreal General Hospital. She said that there are various hypotheses as to why, including animal models that suggest that anti-DNA antibodies could have antitumor effects against certain cancer cell lines (Sci. Transl. Med. 2012;4:157ra142).

"I don’t think this should give us a false sense of reassurance," Dr. Clarke said of the findings, noting that vulvar cancers, likely resulting from HPV infection, were seen as increased in lupus patients and that cervical dysplasia was known to be increased as well.

"I think we still have to screen for breast cancer. And I think that this risk for dysplasia calls us to be even more vigilant than current recommendations," she said.

In a related talk, Dr. Murray B. Urowitz, director of the Centre for Prognosis Studies in the Rheumatic Diseases at Toronto Western Research Institute and a coauthor on both studies, praised Dr. Clarke and colleagues’ malignancy findings as "very important."

"The expected numbers of malignancy in this tremendous number of patients was 561," Dr. Urowitz said at the meeting, referring to the large cohort study. "And the observed number was 644, with the driver being hematologic malignancies." He noted that only age and male gender were found to be predictive factors.

The lower-than expected incidence of hormone-sensitive cancers in the same cohort study, Dr. Urowitz said, was yet another mystery. "Is there a hormonal factor favoring the lupus patient – less total estrogen over her lifetime, less likely to get hormone replacement? Maybe, but the decreased risk seen in SLE is evident in both pre- and postmenopausal lupus. Could it be genetic? It’s unclear. There [are] some very exciting data that anti-DNA antibody may actually be protective, but that’s still in the very early phases."

Dr. Urowitz, Dr. Clarke, and Dr. Bernatsky did not disclose financial relationships bearing on their studies.

BUENOS AIRES – Incidences of certain cancers, particularly lymphomas, have been shown to be higher in people with systemic lupus erythematosus, while hormone-influenced breast, ovarian, and endometrial cancers have recently been found to occur less often in SLE patients than in the general population.

At the 10th International Congress on SLE, the researchers responsible for these findings discussed their implications for clinical practice.

Dr. Ann Clarke of McGill University, Montreal, coauthor of a large case-cohort study that found neither immunosuppressant drug use nor disease activity correlated with lymphoma risk as hypothesized (Ann. Rheum. Dis. 2013 Jan. 8 [doi:10.1136/annrheumdis-2012-202099]), said that clinicians should nonetheless consider a history of malignancies when deciding whether to prescribe immunosuppressants.

The study by Dr. Clarke and her colleagues, led by Dr. Sasha Bernatsky of McGill, enrolled 75 SLE patients with lymphoma and 4,961 cancer-free controls with SLE, seeking to determine associations between lymphoma risk and exposures to cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarials, or steroids. The team also looked at Sjögren’s syndrome, disease duration, and disease activity as potential indicators of risk.

Although cyclophosphamide use was seen more frequently among the lymphoma cases (20%) than in the controls (16.8%), this difference did not reach statistical significance. "There isn’t a strong signal that the drugs are responsible," Dr. Clarke said, but she nonetheless argued for caution in the clinic.

"If there is a remote history of malignancy – more than 5 years, certainly more than 10 – I would proceed [with immunosuppressants]," she said. "If there is a recent history, I would try to avoid them, using rituximab or belimumab as appropriate."

Dr. Clarke’s team, again led by Dr. Bernatsky, also conducted research that examined the incidence of specific cancers in an international cohort of 16,409 patients with SLE (J. Autoimmun. 2013 Feb. 11 [doi:10.1016/j.jaut.2012.12.009]).

This study showed that lupus patients had a threefold higher risk for hematological cancers, especially non-Hodgkin’s lymphoma, and a slightly elevated risk for cancer overall, but saw fewer hormone-sensitive cancers than expected, with the standardized incidence ratio of 0.73 for breast cancers (95% confidence interval [CI], 0.61-0.88), 0.44 for endometrial cancers (95% CI, 0.23-0.77), and 0.64 for ovarian cancers (95% CI, 0.34-1.10).

"There certainly seems to be a convincing signal that female hormone-sensitive cancers appear to be decreased in patients with lupus," said Dr. Clarke, who is also codirector of the lupus clinic at Montreal General Hospital. She said that there are various hypotheses as to why, including animal models that suggest that anti-DNA antibodies could have antitumor effects against certain cancer cell lines (Sci. Transl. Med. 2012;4:157ra142).

"I don’t think this should give us a false sense of reassurance," Dr. Clarke said of the findings, noting that vulvar cancers, likely resulting from HPV infection, were seen as increased in lupus patients and that cervical dysplasia was known to be increased as well.

"I think we still have to screen for breast cancer. And I think that this risk for dysplasia calls us to be even more vigilant than current recommendations," she said.

In a related talk, Dr. Murray B. Urowitz, director of the Centre for Prognosis Studies in the Rheumatic Diseases at Toronto Western Research Institute and a coauthor on both studies, praised Dr. Clarke and colleagues’ malignancy findings as "very important."

"The expected numbers of malignancy in this tremendous number of patients was 561," Dr. Urowitz said at the meeting, referring to the large cohort study. "And the observed number was 644, with the driver being hematologic malignancies." He noted that only age and male gender were found to be predictive factors.

The lower-than expected incidence of hormone-sensitive cancers in the same cohort study, Dr. Urowitz said, was yet another mystery. "Is there a hormonal factor favoring the lupus patient – less total estrogen over her lifetime, less likely to get hormone replacement? Maybe, but the decreased risk seen in SLE is evident in both pre- and postmenopausal lupus. Could it be genetic? It’s unclear. There [are] some very exciting data that anti-DNA antibody may actually be protective, but that’s still in the very early phases."

Dr. Urowitz, Dr. Clarke, and Dr. Bernatsky did not disclose financial relationships bearing on their studies.

BUENOS AIRES – Incidences of certain cancers, particularly lymphomas, have been shown to be higher in people with systemic lupus erythematosus, while hormone-influenced breast, ovarian, and endometrial cancers have recently been found to occur less often in SLE patients than in the general population.

At the 10th International Congress on SLE, the researchers responsible for these findings discussed their implications for clinical practice.

Dr. Ann Clarke of McGill University, Montreal, coauthor of a large case-cohort study that found neither immunosuppressant drug use nor disease activity correlated with lymphoma risk as hypothesized (Ann. Rheum. Dis. 2013 Jan. 8 [doi:10.1136/annrheumdis-2012-202099]), said that clinicians should nonetheless consider a history of malignancies when deciding whether to prescribe immunosuppressants.

The study by Dr. Clarke and her colleagues, led by Dr. Sasha Bernatsky of McGill, enrolled 75 SLE patients with lymphoma and 4,961 cancer-free controls with SLE, seeking to determine associations between lymphoma risk and exposures to cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarials, or steroids. The team also looked at Sjögren’s syndrome, disease duration, and disease activity as potential indicators of risk.

Although cyclophosphamide use was seen more frequently among the lymphoma cases (20%) than in the controls (16.8%), this difference did not reach statistical significance. "There isn’t a strong signal that the drugs are responsible," Dr. Clarke said, but she nonetheless argued for caution in the clinic.

"If there is a remote history of malignancy – more than 5 years, certainly more than 10 – I would proceed [with immunosuppressants]," she said. "If there is a recent history, I would try to avoid them, using rituximab or belimumab as appropriate."

Dr. Clarke’s team, again led by Dr. Bernatsky, also conducted research that examined the incidence of specific cancers in an international cohort of 16,409 patients with SLE (J. Autoimmun. 2013 Feb. 11 [doi:10.1016/j.jaut.2012.12.009]).

This study showed that lupus patients had a threefold higher risk for hematological cancers, especially non-Hodgkin’s lymphoma, and a slightly elevated risk for cancer overall, but saw fewer hormone-sensitive cancers than expected, with the standardized incidence ratio of 0.73 for breast cancers (95% confidence interval [CI], 0.61-0.88), 0.44 for endometrial cancers (95% CI, 0.23-0.77), and 0.64 for ovarian cancers (95% CI, 0.34-1.10).

"There certainly seems to be a convincing signal that female hormone-sensitive cancers appear to be decreased in patients with lupus," said Dr. Clarke, who is also codirector of the lupus clinic at Montreal General Hospital. She said that there are various hypotheses as to why, including animal models that suggest that anti-DNA antibodies could have antitumor effects against certain cancer cell lines (Sci. Transl. Med. 2012;4:157ra142).

"I don’t think this should give us a false sense of reassurance," Dr. Clarke said of the findings, noting that vulvar cancers, likely resulting from HPV infection, were seen as increased in lupus patients and that cervical dysplasia was known to be increased as well.

"I think we still have to screen for breast cancer. And I think that this risk for dysplasia calls us to be even more vigilant than current recommendations," she said.

In a related talk, Dr. Murray B. Urowitz, director of the Centre for Prognosis Studies in the Rheumatic Diseases at Toronto Western Research Institute and a coauthor on both studies, praised Dr. Clarke and colleagues’ malignancy findings as "very important."

"The expected numbers of malignancy in this tremendous number of patients was 561," Dr. Urowitz said at the meeting, referring to the large cohort study. "And the observed number was 644, with the driver being hematologic malignancies." He noted that only age and male gender were found to be predictive factors.

The lower-than expected incidence of hormone-sensitive cancers in the same cohort study, Dr. Urowitz said, was yet another mystery. "Is there a hormonal factor favoring the lupus patient – less total estrogen over her lifetime, less likely to get hormone replacement? Maybe, but the decreased risk seen in SLE is evident in both pre- and postmenopausal lupus. Could it be genetic? It’s unclear. There [are] some very exciting data that anti-DNA antibody may actually be protective, but that’s still in the very early phases."

Dr. Urowitz, Dr. Clarke, and Dr. Bernatsky did not disclose financial relationships bearing on their studies.