Impact of Tumor Progression on Survival during Neoadjuvant Chemotherapy in Breast Cancer: A Cohort Study

doi:10.21203/rs.3.rs-958861/v1

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Impact of Tumor Progression on Survival during Neoadjuvant Chemotherapy in Breast Cancer: A Cohort Study

https://doi.org/10.21203/rs.3.rs-958861/v1

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Background: Although few patients with breast cancer experience tumor progression during neoadjuvant systemic therapy (NST), their extremely poor outcomes are similar to patients who fail to achieve pathological complete response (pCR). No reports have compared patients with pCR, non-pCR, and progression during NST to determine the survival outcomes.

Methods: This retrospective chart review of patients with stage I–III breast cancer was conducted between January 2001 and December 2018. pCR was defined as no invasive cancer or in situ residuals in the breast and lymph nodes (ypT0 ypN0). Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan–Meier methods.

Results: Of the 595 patients who received NST, 167 (29.2%) had pCR (pCR group), 404 (70.8%) responded to NST but did not have pCR (non-pCR group), and 24 (4.0%) experienced tumor progression during NST (PD group). The median DFS was 6.0 months, 154.0 months, and not reached in the PD, non-pCR, and pCR groups, respectively. The PD group had significantly shorter DFS than patients without tumor progression in the pCR and non-pCR groups [hazard ratios (HR) 13.0, 95% CI: 8.1–21.0, p < 0.01]. The median OS was 13.6 months (95% CI: 10.4–35.5) in the PD group and was not reached in the pCR and non-pCR (non-PD) groups. The OS was significantly poorer in the PD group than in the non-PD group (HR 15.8, 95% CI: 9.2–27.1, p < 0.01).

Conclusion: The PD group had the poorest survival outcomes even after recurrence, thus warranting new treatment targets.

Oncology

Breast Cancer

Neoadjuvant Chemotherapy

Tumor Progression during Chemotherapy

Survival Outcome

The concept of preoperative chemotherapy was introduced in 1973 for locally advanced breast cancer [(1, 2)]. The role of neoadjuvant chemotherapy has continued to change over the nearly half century period until today. Recently, neoadjuvant systemic therapy (NST) has become a standard treatment for high-risk early breast cancer or locally advanced breast cancer [(3)]. NST for breast cancer has been established for downstaging tumors and allowing breast-conserving surgery rather than mastectomy. Furthermore, NST can potentially provide an early in vivo response to systemic treatment [(4)]. Therefore, the use of NST has become more common in patients with operable disease [(5, 6)]. Moreover, the 2019 St. Gallen International Breast Cancer Conference recommended neoadjuvant therapy as the preferred treatment approach for stage II/III triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which gives patients the chance to avoid axillary dissection surgery, thus sparing women loss of function and lymphedema and improving long-term outcomes with tailored approaches [(7)].

The role of pathological complete response (pCR) is becoming more important. However, the prognostic significance of pCR after NST remains controversial. Pooled analyses and meta-analyses have shown that pCR has been proposed as a surrogate endpoint for the prediction of long-term clinical benefits, such as disease-free survival (DFS), event-free survival, and overall survival (OS), particularly for triple-negative and HER2-positive breast cancer [(8, 9)]. Given this background, several clinical trials in neoadjuvant settings have defined pCR as the primary endpoint.

Tumor progression during NST is a major concern because tumor upstaging may make breast conservation impossible. Patients who experience tumor progression during NST or who do not achieve pCR have been reported to have a poor prognosis [(10)]. However, no data comparing these three groups (pCR, non-pCR, and tumor progression during NST) have been reported. We aimed to determine the impact of tumor progression during NST on survival and to identify the clinical characteristics of patients with stage I–III breast cancer.

Study design

This retrospective study evaluated the clinical characteristics of patients with stage I–III breast cancer who received NST between January 2001 and December 2018. This study was approved by the Institutional Review Board of the Aichi Cancer Center Hospital, and a prospectively collected database of patients with breast cancer who received NST was established. Data were verified via a retrospective chart review of individual patient records, including age, tumor stage, estrogen receptor (ER) status, progesterone receptor (PgR) status, HER2 receptor status, the presence of lymphovascular invasion, histologic type, and tumor grade.

Progression during NST was defined as any clinical and/or radiographic increase in tumor size or the new development of palpable lymphadenopathy or distant metastasis during treatment. pCR was defined as the absence of invasive cancer and in situ residuals in the breast and in all sampled regional lymph nodes following the completion of NST and no invasive residual disease (i.e., ypT0 ypN0 in the current AJCC staging system) [(11)].

Patient Population And Treatment

All patients had stage I–III breast cancer. The following eligibility criteria were used for this study: histologically confirmed breast cancer, no previous chemotherapy, and adequate organ function. Patients with advanced disease or double cancer were excluded. Patients who had not undergone breast surgery were also excluded. Therefore, 645 patients were initially identified, followed by the exclusion of patients who did not receive NST (n = 23), patients who had metastatic lesions (n = 17), and patients who had double primary cancer (n = 10); the participant selection flow chart is shown in Figure 1.

NST treatment consisted of anthracycline- and/or taxane-based regimens, as determined by the breast oncology team. The patients were evaluated at regular intervals during chemotherapy using physical examinations and radiographic monitoring.

Objectives

The primary objective of this study was to determine the impact of tumor progression during NST on survival compared with pCR and non-PCR groups and to identify the clinical characteristics of patients with stage I–III breast cancer who received NST. This study also assessed the survival outcomes after recurrence for each group (progressive disease [PD], pCR, and non-pCR).

Statistical Analyses

OS1 was calculated from the date of surgery to the date of death from any cause, and OS2 was defined as the time from the first recurrence to the date of death from any cause. DFS was defined as the time from the date of breast surgery to the date of the first event (local, regional, or distant recurrence) or the last follow-up or death. Progression-free survival (PFS) was assessed as the time from tumor recurrence until the first progression event or death.

The patients were divided into three groups. We defined the patients who had pCR as the pCR group, the patients who responded to NST but did not achieve pCR as the non-pCR group, and the patients who experienced tumor progression during NST as the PD group. We assessed the survival outcomes of the three groups. We estimated the hazard ratios (HRs) and 95% CIs of OS and DFS from stratified Cox regression models with study as a stratification factor. The median OS, DFS, and PFS were determined using Kaplan–Meier methods. The statistical analyses were performed with Stata IC 16 software (version 16).

Patient characteristics

A total of 595 patients treated with NST were enrolled in this study. The breakdown of patients is summarized in Figure 2. Of these patients, 167 (29.2%) experienced pCR (pCR group), 404 (70.8%) had non-pCR without tumor progression (non-pCR group), and 24 (4.0%) experienced tumor progression during NST (PD group). The baseline patients and tumor characteristics are listed in Table 1. The three groups had similar median ages. In the PD group, 11 tumors were T4 (46%), 5 were T3 (21%), and 7 were T2 (29%). The tumors tended to be smaller in the pCR and non-PCR groups than in the PD group. This correlation with each group was also found for the node stage. These results indicate that patients in the PD group were more likely to have advanced tumor size stages. However, tumor grade and Ki-67 scores were not much higher in the PD group than in the non-pCR and pCR groups.

Table 1

Patients’ characteristics before neoadjuvant systemic therapy
	pCR		Non-pCR		PD during NCT
		%		%		%
Age (median)	23–77	(50)	29–62	(49)	25–72	(49)
T stage
TX	7	4	3	1	0	0
T1	21	12	36	9	1	4
T2	110	66	239	59	7	29
T3	13	8	47	11	5	21
T4	16	10	79	20	11	46
N stage
N0	59	35	103	25	4	17
N1	89	53	227	56	12	50
N2	10	7	27	7	3	12
N3	9	5	47	12	5	21
TNM stage
I	6	4	13	3	0	0
II	122	73	238	59	7	29
III	39	23	153	38	17	71
Tumor grade
Unknown	6	4	7	2	0	0
1/2	33	20	264	65	5	21
3	128	76	133	33	19	79
Ki-67 score
≤20%	20	12	113	28	3	12
>20%	95	57	187	46	17	71
Unknown	52	31	104	26	4	17
Histology
Ductal	164	98	397	98.3	24	100
Lobular	0	0	2	0.5	0	0
Others	3	2	5	1.2	0	0
Lymphovascular invasion (LVI)
Unknown	139	83	103	25	2	9
Positive	1	1	204	50	22	91
Negative	27	16	97	24	0	0
Menopausal status
Premenopausal	95	57	220	54	6	25
Postmenopausal	67	40	168	42	18	75
Unknown	5	3	16	4	0	0
Subtype
HR+ HER2-	23	14	189	47	8	33
HR− HER2-	43	26	60	15	16	67
HR+ HER2+	32	19	105	26	0	0
HR− HER2+	69	41	50	12	0	0
Treatment
Anthracycline-based	9	5	20	5	1	4
Taxane-based	7	4	23	6	1	4
Anthracycline-taxane	150	90	358	88	21	88
Others	1	1	3	1	1	4

Most patients in the PD group had triple-negative breast cancer (n = 16); the luminal type was found in only eight patients. However, no patients with HER2-positive breast cancer experienced progression during NST. The neoadjuvant chemotherapy regimens were anthracycline-based, taxane-based, and anthracycline followed by taxane. Anthracycline followed by taxane regimens were the most commonly selected regimens, with a similar usage rate in each group (pCR group, 90%; non-pCR group, 88%; and PD group, 88%). All the HER2 breast cancer patients received anti-HER2 treatment plus cytotoxic agents.

Survival Analysis

DFS and OS1 were evaluated during a median follow-up time of 52.2 months (range, 1 to 166 months). Recurrences occurred in 21 of 24 patients in the PD group (87.5%), 97 of 404 patients in the non-pCR group (24.0%), and 6 of 167 patients in the pCR group (3.6%). The median DFS was 6.0 months (95% CI: 4.0–9.5) in the PD group, 154.0 months in the non-pCR group, and was not reached in the pCR group (Figure 3). In the PD group, patients with tumor progression during NST had a significantly shorter DFS than patients without tumor progression in the pCR and non-pCR (non-PD) groups (HR 13.0, 95% CI: 8.1–21.0, p < 0.01). The median OS1 was 13.6 months (95% CI: 10.4–35.5) and it was not reached in the non-PD group. The OS1 was also significantly worse in the PD group than in the non-PD group (HR 15.8, 95% CI: 9.2–27.1, p < 0.01).

Clinical Outcomes After Recurrence

As a secondary analysis, we assessed the survival outcomes after recurrence. A total of 6, 97, and 21 patients in the pCR, non-pCR, and PD groups received first-line systemic therapy, respectively (Figure 2). Twenty-one patients in the PD group experienced recurrence (87.5%). The treatments included chemotherapy, endocrine therapy (46), and radiotherapy after recurrence. In the PD groups, 17 patients (80.9%) received chemotherapy as the first-line treatment, and 3 patients (14.3%) received endocrine therapy.

The median PFS after first-line therapy was 1.9 months (95% CI: 1.0–3.3) in the PD group, 17.8 months in the non-pCR group, and 14.1 months in the pCR group. The PD group had a significantly shorter PFS after the first-line therapy than the non-PD group (HR 4.2, 95% CI: 2.5–7.2, p < 0.01); the same trend was reported in patients with triple-negative or luminal-type breast cancer. The median OS2 time was 8.0 months (95% CI: 5.2–13.1) in the PD group and 51.0 months (95% CI: 33.0–69.3) in the non-PD group (Figure 4). Significantly worse survival outcomes were noted in the PD group compared with the non-PD group (HR 3.6, 95% CI: 2.0–6.4, p < 0.01).

Figure 5 presents a swimmer plot of treatment after recurrence in the PD group. Most patients experienced poor outcomes even after later line treatments. However, triple-negative breast cancer treated with carboplatin had a high efficacy (number 1 in Figure 5), and endocrine therapy with cyclin-dependent kinase (CDK) 4/6 inhibitor or mammalian target of rapamycin (mTOR) inhibitor also had an antitumor effect in a few patients with hormone receptor-positive breast cancer (numbers 16 and 17 in Figure 5).

Our results revealed that tumor progression during NST has a negative impact on survival outcomes. To the best of our knowledge, this is the first report assessing patients divided into three groups (PD group, non-pCR group, and pCR group). The association of tumor progression during NST with poor outcomes was also supported in recurrence settings. Many studies have reported the clinical and molecular predictors of pCR [(4, 12–19)], and pooled analyses and meta-analyses have supported the same findings [(8, 9)]. However, few reports have focused on the predictors of tumor progression during NST. In the literature, cancer progression while receiving NST was reported by the MD Anderson Cancer Center in America [(10)] and the Sunnybrook Odette Cancer Center in Canada [(20)].

Predictive factors of tumor progression during neoadjuvant chemotherapy were reported by Abigail Set al [(10)]. They identified advanced tumor stage, high nuclear grade, high Ki-67 score, and ER/PgR negativity as predictive factors. However, these statuses were also reported as predictive factors for pCR [(21–23)]. The mechanisms or molecular markers that differentiate chemotherapy-sensitive tumors from chemotherapy-resistant tumors are not well known. Furthermore, there are no novel therapeutic targets for patients with tumor progression during NST.

Recently, circulating tumor DNA (ctDNA) has shown an important role in monitoring the early response and predicting survival outcomes after chemotherapy treatment [(24–26)]. The presence of ctDNA has a marked prognostic value when detected after surgical resection [(27)]. Several studies have reported that ctDNA detection at the end of neoadjuvant chemotherapy indicates worse survival outcomes [(28)]. Shunying Li et al demonstrated that ctDNA can be used to predict the tumor response during NST in breast cancer, which may provide personalized treatment with escalating the treatment for the patients with poor outcomes [(29)]. This study showed that the presence of ctDNA before NST was correlated with a worse prognosis, particularly in ER-negative patients. These results suggest that monitoring and detecting ctDNA may help identify the patients with tumor progression during NST.

Enhancing the efficacy of neoadjuvant chemotherapy with immune checkpoint inhibitors might be one of the methods for overcoming primary resistance, which results in the decrease of tumor progression during NST. Two studies in neoadjuvant settings have reported a high response rate to treatment with immune checkpoint inhibitors in a phase 3 trial [(30)-(31)]. These results suggest that there are very large benefits, in terms of pCR, from adding immune checkpoint inhibitors to chemotherapy, particularly in high-risk triple-negative patients, who have a similar status to the patients who experienced tumor progression during NST in our study.

Response-guided therapy with neoadjuvant chemotherapy is the standard strategy for early breast cancer [(32)]. Triple-negative and HER2-positive subtypes are particularly good candidate populations for this strategy, as was shown in the CREATE-X trial [(33)] and KATHERINE trial [(34)]. However, there is no effective therapy for patients with PD during NST. In this study, almost all patients experienced early recurrence and extremely shorter survival regardless of whether they received standard or optional treatment after recurrence in the PD group.

A single institution retrospective study demonstrated the efficacy of salvage therapy for patients with early breast cancer who experience disease progression during NST [(20)]. The salvage treatment includes surgery, concurrent chemoradiation with cisplatin, and chemotherapy alone. They concluded that patients progressing on NST responded well to salvage therapy; however, our study reported poor outcomes in patients with tumor progression during NST compared with those without tumor progression. Interestingly, it was suggested that the efficacy of a platin-based regimen was the same in as our study.

Moreover, one of the differences between the KEYNOTE-522 and IMpassion051 trials is the combination of chemotherapy, specifically whether carboplatin is included. The KEYNOTE-522 trial evaluated treatment including carboplatin and reported a PD rate during neoadjuvant chemotherapy that was lower than in the IMpassion031 trial (1.3% in the KEYNOTE-522 trial vs. 3.0% in IMpassion051 trial) [(30, 31)].

Our study has several limitations. First, this study was a retrospective study conducted based on medical record; therefore, it was difficult to perform multivariable regression analyses to account for potential confounders. Second, this study was performed in a single institution. However, 595 patients were enrolled in this study, which was thought to be a sufficient sample size.

Our findings indicate that the patients who experienced tumor progression during NST had poor survival outcomes with a shorter DFS, and even treatments after recurrence were not sufficiently effective. Future studies are necessary to investigate new target treatments for those with the worst outcomes

ctDNA Circulating tumor DNA

DFS Disease-free survival

ER Estrogen receptor

HR Hazard ratios

NST Neoadjuvant systemic therapy

OS Overall survival

pCR Pathological complete response

PD Progressive disease

PFS Progression-free survival

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of the Aichi Cancer Center Hospital (reception number: 2020-1-504).

Consent for publication

Not applicable.

Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

None.

Authors' contributions

All authors contributed at conceiving and designing the analysis. KN wrote the manuscript. HI participated in revising the manuscript. All authors, including DK, YE, NH, YO, AK, HK, AY, MH, and MS, have read and approved the final manuscript.

Acknowledgements

None.

De Lena M, Zucali R, Viganotti G, Valagussa P, Bonadonna G. Combined chemotherapy-radiotherapy approach in locally advanced (T3b-T4) breast cancer. Cancer Chemother Pharmacol. 1978;1(1):53–9.
Bonadonna G. Karnofsky memorial lecture. Conceptual and practical advances in the management of breast cancer. J Clin Oncol. 1989;7(10):1380–97.
Waks AG, Winer EP. Breast Cancer Treatment: A Review. Jama. 2019;321(3):288–300.
Untch M, Konecny GE, Paepke S, von Minckwitz G. Current and future role of neoadjuvant therapy for breast cancer. Breast. 2014;23(5):526–37.
Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):2483–93.
Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006;24(13):2019–27.
Burstein HJ, Curigliano G, Loibl S, Dubsky P, Gnant M, Poortmans P, et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019. Ann Oncol. 2019;30(10):1541–57.
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.
Spring LM, Fell G, Arfe A, Sharma C, Greenup R, Reynolds KL, et al. Pathologic Complete Response after Neoadjuvant Chemotherapy and Impact on Breast Cancer Recurrence and Survival: A Comprehensive Meta-analysis. Clin Cancer Res. 2020;26(12):2838–48.
Caudle AS, Gonzalez-Angulo AM, Hunt KK, Liu P, Pusztai L, Symmans WF, et al. Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010;28(11):1821–8.
von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–804.
Hess KR, Anderson K, Symmans WF, Valero V, Ibrahim N, Mejia JA, et al. Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol. 2006;24(26):4236–44.
Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11(16):5678–85.
Nolen BM, Marks JR, Ta'san S, Rand A, Luong TM, Wang Y, et al. Serum biomarker profiles and response to neoadjuvant chemotherapy for locally advanced breast cancer. Breast Cancer Res. 2008;10(3):R45.
Zambetti M, Mansutti M, Gomez P, Lluch A, Dittrich C, Zamagni C, et al. Pathological complete response rates following different neoadjuvant chemotherapy regimens for operable breast cancer according to ER status, in two parallel, randomized phase II trials with an adaptive study design (ECTO II). Breast Cancer Res Treat. 2012;132(3):843–51.
Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol. 2002;20(6):1456–66.
Denkert C, Loibl S, Noske A, Roller M, Müller BM, Komor M, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010;28(1):105–13.
Fournier MV, Goodwin EC, Chen J, Obenauer JC, Tannenbaum SH, Brufsky AM. A Predictor of Pathological Complete Response to Neoadjuvant Chemotherapy Stratifies Triple Negative Breast Cancer Patients with High Risk of Recurrence. Sci Rep. 2019;9(1):14863.
Yee D, DeMichele AM, Yau C, Isaacs C, Symmans WF, Albain KS, et al. Association of Event-Free and Distant Recurrence-Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial. JAMA Oncol. 2020;6(9):1355–62.
Raphael J, Paramsothy T, Li N, Lee J, Gandhi S. A single-institution experience of salvage therapy for patients with early and locally advanced breast cancer who progress during neoadjuvant chemotherapy. Breast Cancer Res Treat. 2017;163(1):11–9.
Petit T, Wilt M, Velten M, Millon R, Rodier JF, Borel C, et al. Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Eur J Cancer. 2004;40(2):205–11.
Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer. 2003;88(3):406–12.
Dowsett M, Dunbier AK. Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res. 2008;14(24):8019–26.
Coombes RC, Page K, Salari R, Hastings RK, Armstrong A, Ahmed S, et al. Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence. Clin Cancer Res. 2019;25(14):4255–63.
McDonald BR, Contente-Cuomo T, Sammut SJ, Odenheimer-Bergman A, Ernst B, Perdigones N, et al. Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer. Sci Transl Med. 2019;11:504.
Radovich M, Jiang G, Hancock BA, Chitambar C, Nanda R, Falkson C, et al. Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial. JAMA Oncol. 2020;6(9):1410–5.
Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015;7(302):302ra133.
Cavallone L, Aguilar-Mahecha A, Lafleur J, Brousse S, Aldamry M, Roseshter T, et al. Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer. Sci Rep. 2020;10(1):14704.
Li S, Lai H, Liu J, Liu Y, Jin L, Li Y, et al. Circulating Tumor DNA Predicts the Response and Prognosis in Patients With Early Breast Cancer Receiving Neoadjuvant Chemotherapy. JCO Precis Oncol. 2020;4.
Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020;382(9):810–21.
Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396(10257):1090–100.
von Minckwitz G, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Eiermann W, et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2013;31(29):3623–30.
Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376(22):2147–59.
von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617–28.

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Impact of Tumor Progression on Survival during Neoadjuvant Chemotherapy in Breast Cancer: A Cohort Study

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Abstract

Figures

Background

Methods

Study design

Patient Population And Treatment

Objectives

Statistical Analyses

Results

Patient characteristics

Survival Analysis

Clinical Outcomes After Recurrence

Discussion

Conclusion

Abbreviations

Declarations

References

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