Por: Antônio Luiz Frasson
Presidente da Sociedade Brasileira de Mastologia
O Congresso da Sociedade Americana de Oncologia clinica 2019 começa com um debate sobre o papel da retirada dos linfonodos axilares em mulheres com câncer de mama submetidas à quimioterapia antes da cirurgia. Esta alternativa de tratamento, colocar o tratamento com quimioterapia antes da cirurgia, é importante quando os tumores são do tipo triplo negativo, ou HER 2 maiores de 2 cm, ou com linfonodos positivos. O objetivo nestes casos é iniciar logo o tratamento sistêmico, tornar a cirurgia menos agressiva tanto em relação a mama quanto a axila, e oferecer um tratamento complementar para as pacientes que não apresentarem resposta completa a terapia inicial.
O debate foi em relação à extensão da cirurgia, e a possibilidade de evitar a retirada radical dos linfonodos axilares quando há o desaparecimento completo do tumor neste linfonodos. A sugestão é documentar o desaparecimento da doença, examinando 2-3 linfonodos axilares através da técnica de pesquisa de linfonodo sentinela. Se estes estiverem negativos, não há beneficio em fazer o esvaziamento radical da axila, e as mulheres podem ser poupadas da agressividade deste procedimento. O debate está em como ter esta certeza de que não há mais linfonodos comprometidos, além daqueles retirados com a técnica da biópsia do linfonodo sentinela, principalmente em uma era em que, na presença de resíduo tumoral após a primeira fase de quimioterapia, ainda é possível complementar o tratamento destas pacientes com novos medicamentos disponíveis apenas nos dias atuais, e cuja utilidade não era conhecida antes de 2018.
Minimizar ao máximo o risco de não identificar doença residual após a quimioterapia inicial em pacientes que têm tumores HER2 e triplo negativo, pode permitir acrescentar tratamentos eficazes que permitem melhorar as chances de cura.
Dr. Isabelle Bedrosian
For the last 4 decades, oncologists have been working to reduce the extent of surgery for women with breast cancer without adversely affecting their long-term outcomes. The use of axillary lymph node dissection after neoadjuvant chemotherapy in women who present with node-positive disease is one major area of focus.
“Women with no lymph node involvement gain no benefit from axillary dissection and actually incur risk from the procedure,” said Isabelle Bedrosian, MD, of The University of Texas MD Anderson Cancer Center. “In contrast, knowing which women still have disease in the nodes is important because it helps us understand prognosis and to tailor subsequentreatment.”
Dr. Terry P. Mamounas
According to Dr. Bedrosian, the surgical oncology community generally agrees on the importance of knowing what is going on in a patient’s lymph nodes. The area of some disagreement involves how to accurately identify women who have residual nodal disease following neoadjuvant chemotherapy.
This topic will be debated during an Education Session on June 1, “Debate: Breast Cancer Axillary Management of Nodal Disease in the Neoadjuvant Era: ‘Less Is More’ or ‘More or Less the Same’?”
Dr. Heather B. Neuman
Axillary Dissection for Some.
The original idea behind the use of neoadjuvant chemotherapy was to convert inoperable disease to operable disease, or lessen the extent of surgery by allowing patients to undergo breast-conserving surgery instead of mastectomy, explained Terry P. Mamounas, MD, of NSABP/NRG Oncology and Orlando Health UF Cancer Center. Dr. Mamounas will argue that after neoadjuvant chemotherapy, complete axillary nodal dissection is not indicated for all patients who originally present with node-positive disease.
“Eventually, we realized that we were not only able to eliminate the disease in the breast, but we can also do this successfully in the axillary nodes,” Dr. Mamounas said. “If the nodes normalize after neoadjuvant chemotherapy, we believe that performing sentinel lymph node biopsy [SLNB] without axillary dissection, if the sentinel lymph nodes are negative, is a safe and effective approach for these patients.”
Studies looking into the use of SLNB after neoadjuvant chemotherapy in patients who present with positive nodes before neoadjuvant chemotherapy had false-negative rates between 8% and 14%, Dr. Mamounas acknowledged.1 However, further analyses of the data have shown that by taking certain steps in the performance of sentinel lymph node biopsy, false-negative rates can be much lower.
For example, the false-negative rate decreases if the surgeon removes two or more sentinel lymph nodes and if the combination of isotope and blue dye is used for lymphatic mapping.2,3
Another approach that improves the performance characteristics of SLNB in this setting is to ensure that the previously biopsied positive node is clipped, and the clipped node is removed at surgery, said Heather B. Neuman, MD, of the University of Wisconsin, who, during the session, will present the argument for increased use of SLNB.
“One of the key approaches to is make sure that the node that was biopsied—the clipped node—is now clear of disease,” Dr. Neuman said. “For women with residual disease, those patients still need complete dissection, but we have room to start to spare some women from this larger surgery by using SLNB.”
Axillary Dissection for All
Dr. Bedrosian and Stacey Carter, MD, of Baylor College of Medicine, will present the arguments in favor of complete axillary nodal dissection.
Dr. Bedrosian acknowledged that research into the role of SLNB has come a long way, but she added that more work needs to be done before these techniques—which she labeled sentinel node “plus”—can replace axillary node dissection.
Each of these sentinel node “plus” techniques has only been tested in a limited fashion, in small studies, she said. A multi-institutional randomized clinical trial would be needed to know if the techniques are more broadly applicable.
Before these trials are even conducted though, Dr. Bedrosian said there is more to learn about how other factors might influence SLNB.
“For example, the type of breast cancer a woman has might influence results or how many diseased nodes she had at time of diagnosis,” Dr. Bedrosian said. “The more diseased nodes she started with, the probability of or accuracy of minimally invasive techniques may be lower than if she started with one diseased lymph node.”
Finally, Dr. Bedrosian noted that the high false-negative rates associated with SLNB may have implications for medical management.
“Years ago, if this was wrong, it simply meant we were incorrectly assessing prognosis; there was nothing different we could do treatment wise,” Dr. Bedrosian said. “The field has changed, and studies have shown us that if there is substantial disease after standard neoadjuvant chemotherapy, additional strategies can be employed after surgery that impact long-term survival.”
For example, results of the KATHERINE trial have shown that patients with HER2-positive nonmetastatic breast cancer who have residual invasive disease in the breast or axilla after completing neoadjuvant treatment could reduce their risk for recurrence of death by 50% by undergoing treatment with adjuvant T-DM1 compared with trastuzumab.2
Similarly, the results of the CREATE-X trials showed that adjuvant capecitabine effectively prolonged disease-free and overall survival in women with HER2-negative disease who had residual invasive disease after standard neoadjuvant therapy.3
Role of Radiotherapy
To conclude the session, Chair Reshma Jagsi, MD, DPhil, FASTRO, of the University of Michigan Health System, will discuss the role of adjuvant radiotherapy to the axilla in the management of nodal disease, which has the potential to replace axillary lymph node dissection for local tumor control in some patients who have sentinel-node–positive breast cancer.
– Leah Lawrence
References
Boughey JC, et al. JAMA. 2013;10:1455-61.
Boughey JC, et al. J Clin Oncol . 2015;33:3386-93.
Kuehn T, et al. Lancet Oncol . 2013;14:609-18.
Von Minckwitz G, et al. N Engl J Med. 2019; doi:10.1056/NEJMoa1814017.
Masuda N, et al. N Engl J Med. 2017;376:2147-59.
