‘Very good evidence’ suggests breast implant–associated lymphoma is underdiagnosed

An article published in a British newspaper suggested the number of women at risk for breast implant–associated anaplastic large-cell lymphoma triggered by the most popular type of breast implant used in Great Britain has been greatly underestimated.

The incidence was described as low overall but significantly high when compared with the general population.

Roberto Miranda
Roberto N. Miranda

In the United States, breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) also is rare, with fewer than 100 documented cases to date, according to the FDA. Most cases have a favorable prognosis when diagnosed early and treated appropriately.

HemOnc Today spoke with Roberto N. Miranda, MD, professor in the department of hematopathology at The University of Texas MD Anderson Cancer Center, about the potential risks associated with breast implants, the type of implant that appears most associated with BIA-ALCL, and outcomes for patients diagnosed with this malignancy.

Question: Can you describe the potential cancer risks associated with breast implants?

Answer: This has not been studied systematically. Cancer susceptibility genes or hereditary cancers can be used to determine a patient’s risk, but this type of research for BI-ALCL has not been carried out. There is a case report of one patient who had an inherited mutation of the TP53 gene and BI-ALCL. Although it is possible that this case was just a coincidence, it is also possible that carriers of a cancer susceptibility gene or hereditary cancer have a higher risk for developing ALCL around breast implants. Further, it is telling that half of the reported cases of BI-ALCL have a history of breast cancer and that is why they underwent breast reconstruction with implants. The other half of affected patients had breast implants for cosmetic reasons. However, the denominator for this latter group is very different. As of December, there were about 200 known cases of BI-ALCL, rendering about 100 of these cases among people who had a history of breast cancer, and 100 cases among those who selected breast implants for cosmetic reasons. The denominator for BI-ALCL in the patients who had implants because of breast cancer is approximately 500,000, while the denominator for patients with cosmetic implants is 10 million; thus the frequency for BI-ALCL was more than 10 times higher in women who had breast cancer. This difference may also reflect the fact that patients with breast cancer are followed by oncologists, at least once a year, with the oncologist paying close attention to any abnormality that may suggest recurrent cancer. In comparison, women who have breast implants for cosmetic reasons are not followed systematically, and the diagnosis may occur later.

Q: What role does the type of implant play?

A: Garry S. Brody, MD, a plastic surgeon at University of Southern California, and Mark W. Clemens, MD, FACS, assistant professor of surgery at The University of Texas MD Anderson Cancer Center, have alerted that textured implants — but not smooth, or nontextured implants — appear to be most associated with BI-ALCL. If this finding that smooth implants are not associated with BI-ALCL is confirmed by a more extensive experience, it may be relevant for decision-making.

Q: Is incidence of BI-ALCL underestimated in the United States?

A: We have very good evidence that this type of lymphoma is underdiagnosed. The first manifestation of this lymphoma is usually an effusion or fluid accumulation around the implant that occurs at an average of 8 years after the implantation; not within months, not within 1 year, and maybe not within 2 years. Many plastic surgeons call this ‘seroma,’ which means a fluid accumulation, and it appears that the first entertained diagnosis is that the fluid is associated with a bacterial infection. Patients, therefore, are recommended to receive antibiotics. However, the effusion of BI-ALCL is not infectious. It is usually liquefied tumor necrosis, and unaware of the nature of this fluid, patients sometimes receive aspiration of the fluid through a needle or drainage. This leads to recurrence or progression of disease.

Q: How is a proper diagnosis made?

A: The diagnosis can be rendered when the fluid is sent for pathologic examination. If the fluid or the capsule are sent for pathologic examination, an accurate diagnosis can be rendered. However, because the tumor in its beginning stages can be confined to the fluid, or to a layer of lymphoma cells on the capsule, pathologists may feel uneasy to diagnose lymphoma. These factors may lead to a delayed diagnosis. Although the tumor may recur as effusion again, it may also recur as progression of disease, as in the case reported in the article from the newspaper in Britain. In that case, there is evidence that the diagnosis was delayed and the disease had progressed. The reason the diagnosis was delayed in that particular patient is not known. Maybe it was unsuspected or maybe it was underdiagnosed. When a clinician diagnoses a disease, patients expect to receive adequate therapy. If the disease is not diagnosed properly, the patient will not get the ultimate therapy in a timely fashion, and only after the disease progresses. Underdiagnosing the disease will lead to suboptimal management upfront. Then the disease may recur, and it may recur with disease progression.

Q: What should women consider about cancer risk prior to getting implants?

A: Women may have compounding reasons to have breast implants. Women who have had a history of breast cancer undergo reconstructive surgery for many good reasons, and I would not advise against it. I also think that having breast implants for cosmetic reasons is personal. There is ongoing research that suggests smooth implants as opposed to textured implants may not associate with BI-ALCL; however, these results are preliminary and need confirmation by the medical community. The risk for getting this type of lymphoma is rare. It is probably around 1 per 100,000 women with implants per year.

Q: What is the optimal management of BI-ALCL ?

A: Dr. Clemens is one of the leaders of our multidisciplinary team studying and managing patients with BI-ALCL at MD Anderson Cancer Center. He was the lead author of a study published earlier this year in Journal of Clinical Oncology, in which we show evidence that patients who undergo removal of the implants, plus excision of all of the capsule surrounding the implant or any tumor in the breast, have an excellent outcome. Many of these patients may not even require chemotherapy. The success appears associated with a surgery with negative margins. It is understandable that some patients wish to preserve their implants and opt for chemotherapy instead of surgery, but the role of chemotherapy alone, without surgery, in these patients is not well defined, and it may be lead to recurrence or progression of disease. One would argue that chemotherapy is not the only treatment option. The implants and the tumor all have to be removed even when the tumor is invasive, trying to achieve negative margins. This is what we established in our study. With recurrent disease or progression, patients may undergo replacement of the implant, or removal of the fibrous capsule around the implant.

Q: What a re the typical survival outcomes ? Are they comparable to other lymphoma types?

A: BI-ALCL is comprised of several different types of lymphoma; the name anaplastic lymphoma carries an ominous name, consistent with the initial descriptions of these lymphomas. If patients received combined chemotherapy, survival at 5 years was about 40%. If tumors expressed the protein ALK, survival was as high as 80% at 5 years. Subsequently, a subset of cutaneous lymphomas histologically identical to ALCL were noted to remain confined to the skin. They had a very good prognosis, even without the need of chemotherapy. The last subset of tumors that histologically are ALCL — those described around breast implants — have an excellent prognosis if removed entirely. The 5-year survival rate is more than 90%, usually without a need of chemotherapy if complete surgical resection of the tumor with negative margins is achieved.

Q: Is there anything else that you would like to mention ?

A: BI-ALCL is, in general, underdiagnosed around the world. There is more awareness in the United States, primarily through advocacy groups and the American Society of Plastic Surgeons. Most reported cases are from only 10 countries around the world. Professional societies of pathologists, plastic surgeons and breast oncologists should promote awareness of this lymphoma around the world. This is important because we have evidence that — when the diagnosis of the disease is prompt — the disease can be cured effectively. When diagnosis and therapy are delayed, disease progression occurs. We believe that the most appropriate way to screen for this lymphoma is first to listen carefully to patients and not disregard patients’ symptoms. Ultrasound appears to be the most sensitive technique to detect effusion, whereas PET scan may be more appropriate for preoperative staging. However, treating physicians have to decide this. We suggest that any effusion or capsule mass associated with symptoms after 3 years of initial implantation be analyzed by a pathologist with the hope of detecting the disease at an early stage. – by Jennifer Southall

Reference s :

Clemens MW, et al. J Clin Oncol. 2016;doi:10.1200/JCO.2015.63.3412.

Lee YS, et al. Histopathology. 2015;67:925-927.

www.dailymail.co.uk/health/article-3704934/Cancer-risk-breast-implants-10-times-higher-feared.html

For more information:

Roberto N. Miranda, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030; email: roberto.miranda@mdanderson.org.

Disclosure: Miranda reports no relevant financial disclosures.

An article published in a British newspaper suggested the number of women at risk for breast implant–associated anaplastic large-cell lymphoma triggered by the most popular type of breast implant used in Great Britain has been greatly underestimated.

The incidence was described as low overall but significantly high when compared with the general population.

Roberto Miranda
Roberto N. Miranda

In the United States, breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) also is rare, with fewer than 100 documented cases to date, according to the FDA. Most cases have a favorable prognosis when diagnosed early and treated appropriately.

HemOnc Today spoke with Roberto N. Miranda, MD, professor in the department of hematopathology at The University of Texas MD Anderson Cancer Center, about the potential risks associated with breast implants, the type of implant that appears most associated with BIA-ALCL, and outcomes for patients diagnosed with this malignancy.

Question: Can you describe the potential cancer risks associated with breast implants?

Answer: This has not been studied systematically. Cancer susceptibility genes or hereditary cancers can be used to determine a patient’s risk, but this type of research for BI-ALCL has not been carried out. There is a case report of one patient who had an inherited mutation of the TP53 gene and BI-ALCL. Although it is possible that this case was just a coincidence, it is also possible that carriers of a cancer susceptibility gene or hereditary cancer have a higher risk for developing ALCL around breast implants. Further, it is telling that half of the reported cases of BI-ALCL have a history of breast cancer and that is why they underwent breast reconstruction with implants. The other half of affected patients had breast implants for cosmetic reasons. However, the denominator for this latter group is very different. As of December, there were about 200 known cases of BI-ALCL, rendering about 100 of these cases among people who had a history of breast cancer, and 100 cases among those who selected breast implants for cosmetic reasons. The denominator for BI-ALCL in the patients who had implants because of breast cancer is approximately 500,000, while the denominator for patients with cosmetic implants is 10 million; thus the frequency for BI-ALCL was more than 10 times higher in women who had breast cancer. This difference may also reflect the fact that patients with breast cancer are followed by oncologists, at least once a year, with the oncologist paying close attention to any abnormality that may suggest recurrent cancer. In comparison, women who have breast implants for cosmetic reasons are not followed systematically, and the diagnosis may occur later.

Q: What role does the type of implant play?

A: Garry S. Brody, MD, a plastic surgeon at University of Southern California, and Mark W. Clemens, MD, FACS, assistant professor of surgery at The University of Texas MD Anderson Cancer Center, have alerted that textured implants — but not smooth, or nontextured implants — appear to be most associated with BI-ALCL. If this finding that smooth implants are not associated with BI-ALCL is confirmed by a more extensive experience, it may be relevant for decision-making.

Q: Is incidence of BI-ALCL underestimated in the United States?

A: We have very good evidence that this type of lymphoma is underdiagnosed. The first manifestation of this lymphoma is usually an effusion or fluid accumulation around the implant that occurs at an average of 8 years after the implantation; not within months, not within 1 year, and maybe not within 2 years. Many plastic surgeons call this ‘seroma,’ which means a fluid accumulation, and it appears that the first entertained diagnosis is that the fluid is associated with a bacterial infection. Patients, therefore, are recommended to receive antibiotics. However, the effusion of BI-ALCL is not infectious. It is usually liquefied tumor necrosis, and unaware of the nature of this fluid, patients sometimes receive aspiration of the fluid through a needle or drainage. This leads to recurrence or progression of disease.

Q: How is a proper diagnosis made?

A: The diagnosis can be rendered when the fluid is sent for pathologic examination. If the fluid or the capsule are sent for pathologic examination, an accurate diagnosis can be rendered. However, because the tumor in its beginning stages can be confined to the fluid, or to a layer of lymphoma cells on the capsule, pathologists may feel uneasy to diagnose lymphoma. These factors may lead to a delayed diagnosis. Although the tumor may recur as effusion again, it may also recur as progression of disease, as in the case reported in the article from the newspaper in Britain. In that case, there is evidence that the diagnosis was delayed and the disease had progressed. The reason the diagnosis was delayed in that particular patient is not known. Maybe it was unsuspected or maybe it was underdiagnosed. When a clinician diagnoses a disease, patients expect to receive adequate therapy. If the disease is not diagnosed properly, the patient will not get the ultimate therapy in a timely fashion, and only after the disease progresses. Underdiagnosing the disease will lead to suboptimal management upfront. Then the disease may recur, and it may recur with disease progression.

Q: What should women consider about cancer risk prior to getting implants?

A: Women may have compounding reasons to have breast implants. Women who have had a history of breast cancer undergo reconstructive surgery for many good reasons, and I would not advise against it. I also think that having breast implants for cosmetic reasons is personal. There is ongoing research that suggests smooth implants as opposed to textured implants may not associate with BI-ALCL; however, these results are preliminary and need confirmation by the medical community. The risk for getting this type of lymphoma is rare. It is probably around 1 per 100,000 women with implants per year.

Q: What is the optimal management of BI-ALCL ?

A: Dr. Clemens is one of the leaders of our multidisciplinary team studying and managing patients with BI-ALCL at MD Anderson Cancer Center. He was the lead author of a study published earlier this year in Journal of Clinical Oncology, in which we show evidence that patients who undergo removal of the implants, plus excision of all of the capsule surrounding the implant or any tumor in the breast, have an excellent outcome. Many of these patients may not even require chemotherapy. The success appears associated with a surgery with negative margins. It is understandable that some patients wish to preserve their implants and opt for chemotherapy instead of surgery, but the role of chemotherapy alone, without surgery, in these patients is not well defined, and it may be lead to recurrence or progression of disease. One would argue that chemotherapy is not the only treatment option. The implants and the tumor all have to be removed even when the tumor is invasive, trying to achieve negative margins. This is what we established in our study. With recurrent disease or progression, patients may undergo replacement of the implant, or removal of the fibrous capsule around the implant.

Q: What a re the typical survival outcomes ? Are they comparable to other lymphoma types?

A: BI-ALCL is comprised of several different types of lymphoma; the name anaplastic lymphoma carries an ominous name, consistent with the initial descriptions of these lymphomas. If patients received combined chemotherapy, survival at 5 years was about 40%. If tumors expressed the protein ALK, survival was as high as 80% at 5 years. Subsequently, a subset of cutaneous lymphomas histologically identical to ALCL were noted to remain confined to the skin. They had a very good prognosis, even without the need of chemotherapy. The last subset of tumors that histologically are ALCL — those described around breast implants — have an excellent prognosis if removed entirely. The 5-year survival rate is more than 90%, usually without a need of chemotherapy if complete surgical resection of the tumor with negative margins is achieved.

Q: Is there anything else that you would like to mention ?

A: BI-ALCL is, in general, underdiagnosed around the world. There is more awareness in the United States, primarily through advocacy groups and the American Society of Plastic Surgeons. Most reported cases are from only 10 countries around the world. Professional societies of pathologists, plastic surgeons and breast oncologists should promote awareness of this lymphoma around the world. This is important because we have evidence that — when the diagnosis of the disease is prompt — the disease can be cured effectively. When diagnosis and therapy are delayed, disease progression occurs. We believe that the most appropriate way to screen for this lymphoma is first to listen carefully to patients and not disregard patients’ symptoms. Ultrasound appears to be the most sensitive technique to detect effusion, whereas PET scan may be more appropriate for preoperative staging. However, treating physicians have to decide this. We suggest that any effusion or capsule mass associated with symptoms after 3 years of initial implantation be analyzed by a pathologist with the hope of detecting the disease at an early stage. – by Jennifer Southall

Reference s :

Clemens MW, et al. J Clin Oncol. 2016;doi:10.1200/JCO.2015.63.3412.

Lee YS, et al. Histopathology. 2015;67:925-927.

www.dailymail.co.uk/health/article-3704934/Cancer-risk-breast-implants-10-times-higher-feared.html

For more information:

Roberto N. Miranda, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030; email: roberto.miranda@mdanderson.org.

Disclosure: Miranda reports no relevant financial disclosures.