Neoadjuvant Chemotherapy

            Neoadjuvant chemotherapy (NAC), a pre-operative treatment for breast cancer patients has become increasingly useful. NAC can be used to shrink the tumor in order to be reduced before surgery. Chemotherapy drugs including anthracycline and taxane are used in this treatment.  There have been recent studies focusing on neoadjuvant chemotherapy improving survival rates. NAC treatment is promising but more studies should be conducted in order to be implemented through different subsets of breast cancer patients.

Neoadjuvant chemotherapy is able to provide potential benefits if patients qualify for this treatment before surgery. Furthermore, the addition of pCR (pathologic complete response) has become a predictor of future outcomes. Several reports regarding NAC treatment has focused on its ability to improve the overall survival rate.

NAC studies are widely used on triple negative breast cancer patients. This is mainly due to the reason that TNBC is a very aggressive type with low survival rates. Since they showcase poor outcomes, the regimens used in NAC provide the attempt to improve survival rates among TNBC patients. Although TNBC is chemo-sensitive, there is no clear indication that this portrays overall survival rates through NAC treatment. In Fisher’s et al ¹ article, “Neoadjuvant Chemotherapy Is Associated with Improved Survival Compared with Adjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer Only after Complete Pathologic Response”, its study focuses on TNBC patients receiving NAC along with pCR treatment. Their retrospective study consisted of 385 TNBC patients with stages I-III. According to their data, 92.3% of the patients who received pCR after NAC, portrayed an overall survival rate. Fisher et al states, “we show a clear benefit of neoadjuvant chemotherapy in those patients with pCR but again confirm our previous findings that there is a subset of patients…”¹ Although their findings show the benefit of enhancing NAC with pCR, they cannot make a generalization of NAC improving survival rates since they only studied on TNBC patients. Therefore, they do acknowledge that it remains unclear whether NAC improves the overall survival for this particular subset and others. This might be viewed as controversy among NAC treatment because this study did not fulfill the objective by concluding on the survival rate. However, their study indicates a promising number for the TNBC patients, resulting in positive results with NAC treatment. This study indicates a positive step into analyzing the overall rate of treating patients with NAC along with pCR afterwards.

Furthermore, Fisher, et al clearly depict the advantage of combining NAC with pCR. In their study, they portrayed the benefit among the TNBC patients. They also emphasize on patients that didn’t encounter pCR, had poorer outcomes compared to the individuals that did. This might be viewed as a strong indicator that pCR is an extra phase in a patient’s diagnosis in order to improve survival rates. Their findings make the study more reliable and initiates ways to enrich NAC treatment with the contribution of pCR. Furthermore, their study acknowledges the limitations but conclude that NAC and pCR provide outcomes that actually improve survival among TNBC patients. Although, this study had a few limitations, it’s a reliant research study that should be conducted consecutively in order to support the overall survival.

Similarly, Biswas et al ² examined the effect of NAC treatment and pCR among advanced stage triple negative breast cancer patients. In their article, “The survival benefit of neoadjuvant chemotherapy and pCR among patients with advanced stage triple negative breast cancer”, consisted of 452 TNBC patients and evaluates the impact of NAC treatment. The limitations of this study was the lack of knowledge on pCR following NAC treatment. This setback might introduce controversy because they don’t have the necessary knowledge to analyze the results of pCR involvement with NAC treatment. Although, they were able to analyze the results, a further analysis should be conducted. The most commonly regimens used in this treatment were taxane and anthracycline; 31% of TNBC patients achieved pCR along with the enhancement of the drugs mentioned in this study.

Biswas et al study generates available data on superior survival outcomes of pCR. Biswas et al states, “that achieving pCR provides an important surrogate marker for predicting long term clinical response and survival outcome”². Researchers portrayed the clear indication of pCR as an effective method for improving lifelong outcomes for patients. Their results emphasize on how patients can benefit from pCR for an overall benefit. Regarding their limitation previously discussed, they were still able to identify pCR as a way to produce effective survival rates through their research data. While this study did not conclude on the survival rate, they depict the use of pCR with NAC treatment as a strong indicator.

It is still not well established if whether NAC treatment is able to improve the TNBC cohort survival rates. Biswas et al ² suggests a different approach in order to improve the rate of pCR in aggressive TNBC. Specifically, novel strategies by introducing a different method other studies can use. Certain approaches such as evaluating different subsets of breast cancer with a large sample size. It’s important to acknowledge that every patient’s diagnosis is different and stating the impact for a particular subset doesn’t do much for other groups. If more studies were to be conducted, clinical researchers would be able to provide different mechanisms for patients.

In Guiu et al ³ article, researchers provide knowledge on overall survival rates after NAC treatment and pCR rates among TNBC patients. The limitations of this study consisted of a fairly small sample size of 46 patients and potential selection bias. In Guiu et al article, “Neoadjuvant chemotherapy for triple negative breast cancer: pathologic complete response and survival after long-term follow up “, their results portrayed middling numbers. They were able to conclude that between a 2 and 10-year rate, the overall survival was 53.7% while the pCR rate was 28.2%. Guiu et al states, “overall survivals are lower than in non-triple negative breast cancer, thereby confirming the worst prognosis of TNBC” ³. Although the pCR rate is consistent compared to other studies I researched, the survival rate is somewhat low. There is a lack of attention towards the process of the study and that needs to be acknowledged. Specifically, using a small sample size wasn’t the best idea and led to the lack of a positive inference regarding NAC improving rates. Based off their conclusion and study results, more studies need to be conducted.

In Zhang et al ⁴ study, they clearly indicate the combination of NAC treatment and pCR as a viable strategy. This retrospective study consisted of 119 locally advanced breast cancer patients with short follow- up time. In Zhan et al article, “The efficacy of neoadjuvant chemotherapy for HER-2-positive locally advanced breast cancer and survival analysis”, researchers analyzed the contributing factors in NAC treatment. Although their study did not go into depth of the results, instead they focused on the overall procedure. They discuss high significance on the regimens used specifically, trastuzumab. Zhang et al states, “with the availability of trastuzumab, which has been widely reported to improve the pCR rate from 30.3% to 65& when used as a part of NAC regimen” ⁴.  With high emphasis on regimens used in NAC treatment, it has helped boost the prognosis of pCR and its rate. This study takes a different approach compared to others but they state key points. They decided to focus on what occurs during this therapy by analyzing the drugs used and pCR involvement. Although this research study isn’t the strongest, their data is definitely something to acknowledge and should be conducted for a larger sample size. The researchers suggest on more attention regarding trastuxumab and pCR in order to increase the rate. They indicate some type of importance between these significant factors but also acknowledge their limitations.

In Cliffton et al ⁵ study, researchers analyze the benefits of adjuvant versus neoadjuvant in TNBC patients. Their retrospective study consisted of 4027 TNBC patients with stages I-III. In Cliffton et al study, “Adjuvant versus neoadjuvant chemotherapy is triple negative breast cancer patients with BRCA mutation”, researchers emphasize on the overall survival among the patients. This study incorporated regimens including anthracycline and taxane. According to their results, they portrayed a strong indication of the overall survival rates regarding neoadjuvant chemotherapy in the cohort through the use of the regimens. However, they do acknowledge that more studies should be conducted to evaluate the overall survival by using different agents. Since this study was a fairly large sample, their results depicted a clear overall survival for TNBC patients. By focusing on the drugs used in NAC treatment, they successfully stated the overall survival. The researchers saw the clear advantage of the agents used for this particular study and suggested for different drugs to be tested. This is the strongest article I was able to research on and shows there are different approaches on how researchers can portray the improvements of survival rate through the use of NAC treatment.

In Prat et al ⁶ study, the researchers exemplified a clear stance on opposing NAC treatment. The study consisted of 957 breast cancer patients treated with anthracycline and taxane. In the Prat et al study, “Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy”, the researchers mainly focused on predicting survival from NAC treatment. Prat et al states, “If the main objective of neoadjuvant chemotherapy is to increase survival, then these patients with an outstanding baseline prognosis should be spared the toxic side-effects of chemotherapy and undergo surgical removal of their tumors”. ⁶ This is a counterargument for my previous study, they completely go against the regimens used and portray no significance in them. From their research, they were able to conclude that the chemotherapy drugs are very toxic and does not recommend this therapy for patients. Prat et al research data is evidently opposed of neoadjuvant chemotherapy survival rates and provided valid assertions. Prat concluded that the survival benefit for patients using NAC treatment was significantly low. This was an important study for me to conclude because Prat et al introduced a different perspective for readers to acknowledge.

NAC treatment is very complex and technical. While, all of them concluded that more studies should be conducted, they all took different approaches to improve the survival rate. Most of them had limitations, which set them into a middling discussion. It’s important to acknowledge the pattern of the studies because they portray trial and error.

I was able to provide different methods on how studies can improve survival rates. While, their data was reliant, they were not able to conclude on NAC improving survival rates because one study isn’t enough. Furthermore, I also focused on strong research within the association of pCR and regimens used for NAC treatment. Through the combination of these significant factors, it made the research data more convincing and portrayed the improved survival rates. Neoadjuvant chemotherapy is on the verge on improving survival rates.

Works cited

1. Fisher, C.S., Ma, C.X., Gillanders, W.E., Aft, R.L., Eberlein, T.J., Gao, F., Margenthaler, A. Neoadjuvant chemotherapy is associated with improved survival compared with adjuvant chemotherapy in patients with triple-negative breast cancer only after complete pathologic response. Ann Surg Oncol (2012);19: 253-258.
2. Biswas, T., Efird, J., Prasad, S., Jindal, C., Walker, P. The survival benefit of neoadjuvant chemotherapy and pCR among patients with advanced stage triple negative breast cancer. Oncotanget (2017); 8:112712-112719.
3. Guiu, S., Arnould, C., Coudert, B., Liegard, M., Mayer, F., Faveier, L., Fumoleau, P. Neoadjuvant chemotherapy for triple negative breast cancer: pathologic complete response and survival after long-term follow up. Cancer Research (2009); 69:10-13.
4. Zhang, W., Tian, H., Yang, S. The efficacy of neoadjuvant chemotherapy for HER-2- positive locally advanced breast cancer and survival analysis. Analytical Cellular Pathology (2017);2017: 1-5.
5. Cliffton, K., Barrera, A.G., Roland, J.M., Bassett, J., Litton, J., Kuerer, H., Moulder, S., Albarracin, C., Hortobagyi, G., Arun, B. Adjuvant versus neoadjuvant chemotherapy in triple-negative breast cancer patients with BRCA mutation. Breast cancer research and treatment (2018); 1-9.
6. Prat, A., Fan, C., Fernandez, A., Hoadley, K., Martinello, R., Vidal, M., Viladot, M., Pineda, E., Arance, A., Munoz, M., Montserrat, Pana, L., Cheang, M., Adamo, B.,Perou, C. Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy. BMC Medicine (2015).