Preoperative dose-dense docetaxel and cyclophosphamide alternating with epirubicin and cisplatin(ddDCEP): an effective, novel way of incorporating platinum in the treatment of early TNBC

doi:10.21203/rs.3.rs-1519744/v1

Purpose

Carboplatin-containing treatment regimens in early TNBC have shown improved pCR(pathological complete response) and better EFS(event-free survival) but at the expense of increased toxicity, often leading to compromised delivery of planned treatment. We aimed to evaluate a novel alternating regimen to incorporate platinum in early TNBC.

Methods

We analyzed the data of women with early TNBC who were treated with four cycles each of docetaxel(D;75 mg/m2) and cyclophosphamide(C;600 mg/m2) alternating with cisplatin(P;60 mg/m2) and epirubicin(E;90 mg/m2) (ddDCEP) given every two weeks over a duration of 16 weeks. Pathological complete response was the primary endpoint assessed, along with treatment delivery, adverse events, and survival.

Results

A total of 116 women with stage I-III TNBC received neoadjuvant ddDCEP. Pathological complete response(pCR) defined as no residual invasive cancer in both breast(T0/Tis) and axilla(N0), was observed in 55.2% of all evaluable patients. The proportion of pCR in stage I/II disease was 62.2%, and stage III was 49.5%. 37.9% of patients developed grade 3 anaemia. Grade 3/4 neutropenia occurred in 16.3%, and febrile neutropenia in 4.3% of patients. 86% of patients completed all 8 cycles of chemotherapy, and 98% at least 6 out of 8 cycles. 12% of patients required a dose reduction of taxane, 13% for epirubicin, and 19% for platinum. The proportion of patients requiring dose reduction and the average total dose reduction was significantly higher in the pCR compared to the no pCR group for cisplatin and epirubicin. At 2 years of median follow-up, the recurrence-free survival was 91.2%, and overall survival was 97%.

Conclusion

In non-metastatic TNBC, treatment with ddDCEP as neoadjuvant therapy resulted in a high pCR(55.2%) proportion allowing good delivery of all planned therapy with manageable toxicity.

Triple-Negative Breast Cancers

Breast Cancer

cis-Platinum

cis-Diamminedichloroplatinum(II)

Neoadjuvant Chemotherapy

Pathological Complete Response

ddDCEP

alternating chemotherapy

Pathological complete response(pCR) is associated with better survival in triple-negative breast cancer (TNBC)
A new regimen administering four cycles each of docetaxel and cyclophosphamide alternating with cisplatin and epirubicin every two weeks over 16 weeks (ddDCEP), resulted in pCR of 55.2% in stage I-III TNBC
This regimen was well tolerated with good treatment completion rates and low incidence of grade 3/4 adverse events, especially febrile neutropenia
ddDCEP could be an optimal method of platinum delivery and could serve as an effective chemotherapy backbone for checkpoint inhibitors preoperatively to maximize pathological response

Triple-negative breast cancer (TNBC) comprises up to 17% of all breast cancers worldwide.(1) The five-year net survival for breast cancer in India stands at 60%, in stark contrast to the 85–90% survival reported in the developed world.(2–5) Although the treatment landscape of early TNBC is rapidly evolving with the addition of checkpoint inhibitors(6) and poly(ADP-ribose) polymerase(PARP) inhibitors(7), the single-agent activity of platinum salts(8) and the implication of the homologous recombination repair pathway deficiency(HRD) in the pathogenesis of TNBC(9, 10), have led to a growing interest in evaluating these drugs in early-stage disease.(9)

Carboplatin has improved pCR in multiple randomised trials and EFS in two of them.(7) At the same time, it has increased toxicity, resulting in reduced delivery of all planned chemotherapy doses.(11) A recently updated meta-analysis, which included 6 RCTs, has confirmed the EFS gain from the addition of platinum for early-stage TNBC.(12)

The pCR rates with cisplatin, when used as a single agent or in combination therapy, range from 18–62%.(13–17) However, data supporting the use of cisplatin-based combination chemotherapy, especially in patients with locally advanced TNBC, is limited.

We chose cisplatin over carboplatin, considering the lower incidence of myelotoxicity with it, which could, in turn, maintain dose density, intensity and complete delivery of planned doses. We studied the efficacy and safety of a novel schedule of alternating dose-dense neoadjuvant chemotherapy incorporating cisplatin in TNBC and report our outcomes.

Design and patient selection

This was a single-arm retrospective cohort study done at a tertiary teaching hospital in South India. From Jan 2017 to Jan 2020, 116 consecutive patients with early or locally advanced triple-negative breast cancer who had good performance status consented to receive the novel ddDCEP regimen as neoadjuvant therapy.

Inclusion criteria were histologically confirmed invasive triple-negative breast cancer(< 1% tumour cells positive for oestrogen and progesterone receptors and Her2 neu immunohistochemistry(IHC) score of 0 or 1 + or ISH(in-situ hybridisation) negative if 2+/equivocal by IHC) and performance status of ECOG 0–2.

All data for the retrospective analysis were collected from the hospital’s electronic medical records system and paper records. Patients were staged according to the 7th edition of the AJCC/UICC staging manuals. Patients were prospectively followed up to assess relapse and survival events. The study was approved by the ethics committee(Institutional Review Board) of the Christian Medical College, Vellore (CMC IRB Min. No. 13960 [Retro]). All participants in this study had given written informed consent to undergo treatment with the ddDCEP regimen. As this was a retrospective analysis, consent for publication was waived by the institutional review board.

Treatment

Patients received docetaxel(D;75 mg/m2) and cyclophosphamide(C;600 mg/m2) given in cycles 1, 3, 5 and 7 alternating with cisplatin(P;60 mg/m2) and epirubicin(E;90 mg/m2) given in cycles 2, 4, 6 and 8. The cycles were administered every two weeks with pegfilgrasitim support over a total duration of 16 weeks. Patients underwent mastectomy or breast conservation surgery depending on patient preference and feasibility as assessed by the surgeon. Following surgery, patients received adjuvant radiation therapy, if indicated. Patients with residual disease in the resection specimen were offered adjuvant capecitabine for 6–8 cycles.

Outcomes and follow-up

The primary outcome of interest was the proportion of patients who had pathological complete response following neoadjuvant chemotherapy with the ddDCEP regimen. Secondary outcomes assessed included adherence to planned chemotherapy cycles, dose reduction, dose omissions, disease-free survival (DFS), and overall survival (OS). Adverse events were graded in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

Response to chemotherapy, as seen in the surgical specimen, was graded by the pathologist based on the Miller-Payne and TNM systems. Pathological complete response was defined as no residual invasive cancer in the breast or axilla(ypT0/Tis, N0).(18) Miller Payne response grades of 3 and 4 were classified as “good pathological response” to therapy. The pCR in breast alone and axilla alone were analysed separately.

Patients were followed up for DFS and OS events by a telephonic interview. In those who could not be contacted over the telephone, the most recent out-patient visit was taken as the last point of follow-up. The data cut-off was in November 2021.

Statistical analysis

We estimated that a sample size of 93 patients would confer a power of 90% at a 1-sided alpha of 0.05, to detect the expected increase in pCR proportion of 15%, in comparison with historical cohorts treated with anthracycline-taxane chemotherapy (alternative hypothesis pCR proportion of 0.5; null hypothesis pCR proportion of 0.35 from previous pooled analysis).(19, 20) The expected proportion was estimated from a previous study of preoperative cisplatin carried out at our centre.(21)

Survival analysis was done using the Kaplan-Meier method and comparison between groups using the Cox-Mantel log-rank test. Disease-free survival (DFS) and overall survival(OS) were calculated from the time of diagnosis. Univariate and multivariate analysis was done to identify factors associated with pCR. A p-value of less than 0.05 was considered statistically significant. Data entry was done using Epi Info v7.2.3.1 and analysed using IBM SPSS Statistics v23 and R R v4.0.0.

Patient characteristics

A total of 116 women with non-metastatic TNBC received neoadjuvant ddDCEP chemotherapy from January 2017 to January 2020, with a mean age of 44.5 years. The baseline characteristics of the patients included are summarised in table 1. Locally advanced disease(Stage III) was present in 60 out of 107(56.1%), including N3 disease in 6(5.2%) patients. Seven patients(6.5%) had stage IIIC disease. Two-thirds of the patients had grade 3 tumours and 12% had HER2 low(IHC 1+/2+, ISH negative) tumours. Among the 116 patients included in the study, 7 patients had lumpectomy prior to presentation to our centre, 1 patient did not consent for surgery after chemotherapy, 2 had surgery at another centre due to logistical reasons during the COVID-19 pandemic, and 1 patient died before surgery at another centre. Breast conservation surgery following NACT was done in only 13.5% of patients, and the rest underwent mastectomy.

Outcomes

Of 116 patients on NACT, 105 (90.5%) had surgical histopathology evaluable for post-chemotherapy response. pCR, defined as no residual invasive cancer in both breast(T0/Tis) and axilla(N0), was observed in 55.2% of the evaluable patients (Table 2). The pCR proportion was highest with stage I disease (100%), followed by stage II(59.5%) and stage III(49.5%). Among patients who had clinical or radiological evidence of node-positive disease at baseline, 80% had nodal PCR after neoadjuvant ddDCEP. Miller Payne grade 5 pathological response was seen in 60% of patients. Good partial response (Miller Payne grades 3 and 4) was observed in 31.7% of patients. pCR proportion was numerically higher among patients with grade 3 tumours(57.1%) as opposed to grade 1/2 tumours(48.4%) (p-value 0.42). pCR proportion among those with HER2 negative(score 0 by IHC) was numerically higher at 57.6% as compared to those with HER2 low expression(1+/2+ by IHC with ISH negative) at 38.5%(p-value 0.16). Patients with neutropenia grade 3/4 has a higher odds of attaining pCR in univariate analysis (OR 2.93[0.98-8.78], p-value 0.04). In a multivariate logistic regression model incorporating 5 independent variables, higher grade of neutropenia remained significantly associated with a higher chance of pCR in this cohort(p-value 0.047)(Table 3).

The median duration of follow-up was 24.03 months(IQR 14.25- 29.46). At 24 months of follow-up, the disease-free survival was 91.2%(95% C.I 0.86-0.97), and overall survival was 97% (95% C.I 0.93-1.00). The disease-free survival for those with and without pCR was 90.5%(95% C.I 0.82- 0.99) and 84.2%(95% C.I 0.72-0.98) respectively, at 36 months(log-rank p-value 0.665).(Figure 1A) The At data cutoff, among patients evaluable for pCR, with a total of 9 RFS events(4 in the PCR group and 5 in the no PCR), this difference did not reach statistical significance. Median survival has not been reached for either group.

Adverse events

Anaemia was the predominant haematological toxicity.(Table 4) At baseline, 47.4% had anaemia (WHO definition)(22), highlighting the high prevalence of anaemia in this population of Indian breast cancer patients. During chemotherapy, 37.9% of patients developed CTCAE v4.0 grade 3 anaemia.

The median baseline hemoglobin was 12.1 g/dL(IQR 10.9-12.7 g/dL), median lowest hemoglobin was 8.3 g/dL(IQR 7.6-9.3 g/dL) and median post-chemotherapy hemoglobin was 9.3 g/dL(IQR 8.5-10.1 g/dL).(Figure 2A) 37.9% of patients required transfusion of at least one unit of packed red cells(indications were Hb<8g/dL or anemia in heart failure). The incidence of thrombocytopenia was 63% overall, with grade 3/4 being 8.6%. Grade 3/4 neutropenia was seen in 16.3% of patients, with febrile neutropenia occurring in 4.3%. Nine patients developed grade 1/2 acute kidney injury (AKI) attributable to cisplatin administration which resolved with hydration, and none required dose omissions of cisplatin or delay in chemotherapy. There were no patients with grade 3/4 renal toxicity, hearing loss or tinnitus.

Nausea and vomiting were documented in 25.9% of patients, and clinically significant peripheral neuropathy was reported in 7 patients (all grade 1/2). The neuropathy did not warrant dose omission.

Treatment delivery

Delivery of 6 out of 8 planned cycles (75% of all agents) was achieved in 98% of patients, and all 8 cycles in 85%. (Figure 2B) This translates to 91% dose completion for DC(docetaxel- cyclophosphamide) and 86% dose completion for EP(epirubicin- cisplatin). Twelve per cent of patients required a dose reduction in docetaxel, 13% required dose reductions in cyclophosphamide and epirubicin and 19% required dose reductions in cisplatin. Among the patients who required a dose reduction, the median dose reduction was 25%(IQR 6-25) for docetaxel, 12.5%(IQR 1-25) for cyclophosphamide, 25%(IQR 6-28) for epirubicin and 20%(IQR 6-25) for cisplatin. The average total dose reduction was significantly higher in the pCR vs. no pCR group for cisplatin(5.2% vs. 1.4%; p-value 0.01) and epirubicin(3.7% vs. 1.2%; p-value 0.03)(Figure 3A). The difference in the proportion of patients who had dose reduction in epirubicin and cisplatin between the pCR and no pCR groups was also statistically significant (Figure 3B).

Pathological complete response(pCR) following neoadjuvant chemotherapy is a strong surrogate end-point, predicting better survival outcomes in TNBC.(23) The CTNeoBC pooled analysis, as well as another meta-analysis of 27,895 patients both, found a strong association between pCR and OS.(24, 25) A more recent meta-analysis, however, which took into account 54 randomised trials comprising data of 32,611 patients has cast doubt on the surrogacy of pCR at the trial level for disease-free survival and overall survival, even in the TNBC subgroup.(26) Notwithstanding the controversy, with the current standard of care of dose-dense anthracycline and taxane-based NACT in most centres worldwide, the expected pCR ranges from 31 to 33.6%, as reported in pooled analysis.(23) This low pCR proportion is probably due to a large proportion of patients presenting with node-positive or locally advanced disease in regions lacking screening and early detection facilities.(2, 27, 28)

The necessity for higher pathological response rates and better survival outcomes in these patients led to the current study evaluating the efficacy and safety of the neoadjuvant ddDCEP chemotherapy regimen designed to enable safe, dose-dense delivery of a platinum salt along with the other active agents in early TNBC.

The addition of neoadjuvant carboplatin to anthracycline, taxane and cyclophosphamide has improved pCR rates to 46–59% in the GeparSixto, CALGB 40603, ADAPT-TN, GeparOcto and BrighTNess trials.(7, 11, 29–31) However, improvements in event-free survival have been inconsistent, seen only with the GeparSixto and BrighTNess trials. No trial has demonstrated an overall survival benefit thus far, probably due to inadequate sample size to detect an effect. Hence, the debate on the use of carboplatin preoperatively in early TNBC continues and is optional across guidelines proposed by various professional societies.(32, 33) This apparent lack of survival benefit in the carboplatin trials could be attributed to the significantly higher grade 3/4 haematological toxicity leading to dose omissions, especially of the other drugs in the regimen.(7) Thus, the benefit of increased pCR might be offset by the inability to deliver all the planned doses of active agents.

Cisplatin being less myelotoxic than carboplatin could mitigate the hematologic toxicity attributable to the addition of carboplatin to weekly paclitaxel, thus increasing treatment compliance and maintaining dose-density.(34) There are no randomised trials comparing carboplatin with cisplatin in early breast cancer. However, a retrospective study of 144 patients by Hurley et al. comparing carboplatin and cisplatin in locally advanced TNBC showed a possible survival advantage with the use of the latter.(15) The safety of cisplatin in early TNBC has been explored previously. The INFORM phase II randomised trial(TBCRC 031) compared cisplatin with doxorubicin-cyclophosphamide(AC) NACT in HER2 negative breast cancer patients. Cisplatin given at 75mg/m2(3 weekly) was well-tolerated with a good safety profile. In the ddDCEP regimen, we used cisplatin 60mg/m2 of at an interval of 4 weeks. The TBCRC 030 phase II randomised trial compared preoperative cisplatin vs paclitaxel monotherapy in 139 TNBC patients with HRD and found similar PCR rates(26.4% and 22.3%, respectively) with an acceptable safety profile.

Our experience prior to using the current regimen in administering sequential cisplatin every 3 weeks with paclitaxel following doxorubicin and cyclophosphamide saw nearly 51% of patients having dose omissions.(21) The new regimen was designed with a relatively low dose of cisplatin, targeting a cumulative dose of 240 mg/m2 over 16 weeks. The cisplatin was administered concurrently with epirubicin rather than the taxane to reduce overlapping neurotoxicity. It incorporated four active chemotherapy agents in TNBC in a dose-dense 2-weekly schedule.

We also hoped to improve treatment delivery by administering non-cross-resistant drugs with non-overlapping toxicity concurrently, in an alternating schedule.(35, 36) The regimen in this study also has fewer hospital visits than the weekly regimens and was well-tolerated with higher dose completion and fewer adverse events as compared to the GeparSixto and CALGB trials. The CALGB 40603 trial with carboplatin added to anthracycline, taxane, and cyclophosphamide has reported high rates of grade 3/4 neutropenia (57%) and febrile neutropenia (12%), which require significant resources to manage and increases the overall cost of treatment. Thirty-six percent of patients missed > = two doses of paclitaxel, 26% required dose reduction of paclitaxel and 22% required dose reduction in AC. The delivery of the platinum also proved difficult, with 20% of patients not receiving all 4 doses of carboplatin. The GeparSixto regimen also had high rates of grade 3/4 hematologic toxicity and nearly 50% treatment discontinuation in the carboplatin arm. In our study, the treatment delivery with the ddDCEP regimen was comparatively better, with only 9% of patients missing a dose of docetaxel and only 12% requiring a dose reduction. Haematological toxicity, specifically neutropenia and febrile neutropenia, was also low. We attribute this to the alternating schedule of administration, the interval of 4 weeks between doses of individual drugs, and the relatively lower dose of cisplatin.

A high proportion of patients(55.2%) had PCR when treated with this 2-weekly alternating regimen, comparable to the PCR rates seen in the previously mentioned carboplatin trials.(6, 7) The long-term survival outcomes with this regimen however remain to be seen, as the follow up is currently short. A detailed analysis of anemia, transfusion requirement, predictors of severe anemia and financial burden due to transfusion in this cohort of patients has been reported previously.(37)

Our study does have its limitations, primarily due to its retrospective design. The clinical toxicity data (nausea, vomiting, neuropathy) collected from the electronic medical records is most likely an underestimate of the actual figures due to under-reporting. This was a non-randomized, single-arm study, and direct comparison with respect to survival and efficacy cannot be drawn with historical cohorts of patients who received anthracycline and taxane chemotherapy nor with the randomised trials of carboplatin. This regimen should be evaluated in a randomised trial in the near future.

The alternating ddDCEP regimen resulted in pathological complete response in 55.2% of patients with good tolerance and a majority(86%) completing all planned doses. This proportion of pCR is higher than historical data with anthracycline-taxane therapy and comparable to carboplatin. The major adverse effects were haematological, predominantly anemia, with febrile neutropenia occurring in 4% of patients. Further follow-up is required to determine the long-term survival of these patients, especially those with residual disease. The efficacy results of this study are reassuring and merit further evaluation of this chemotherapy backbone alone or in combination with checkpoint inhibitors in future randomised trials.

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Data Availability

The datasets generated during and/or analysed during the current study are not publicly available due to institutional policy, but are available from the corresponding author on reasonable request

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Ethics approval

The study was approved by the ethics committee (Institutional Review Board) of the Christian Medical College, Vellore (CMC IRB Min. No. 13960 [Retro]).

Consent to participate

Informed consent was obtained from all individual participants included in the study to receive the ddDCEP chemotherapy regimen.

Consent to publish

As this was a retrospective analysis, consent for publication was waived by the institutional ethics committee/review board.

Author Contributions

CRediT author statement

Ashish Singh: Conceptualization, Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization, Supervision, Project administration, Funding acquisition

Josh Thomas Georgy: Conceptualization, Methodology, Formal analysis, Investigation, Writing -

Original Draft, Visualization

Ajoy Oommen John: Conceptualization, Methodology, Formal analysis, Writing - Review & Editing, Visualization

Divya Bala Thumaty: Conceptualization, Methodology, Formal analysis, Investigation, Writing -

Review & Editing, Visualization

Anjana Joel: Conceptualization, Methodology, Formal analysis, Investigation, Writing- Review & Editing, Visualization, Supervision

Parth Sharma: Methodology, Formal analysis, Investigation, Writing – Original Draft

Anand Andrews: Methodology, Formal analysis, Investigation, Writing – Original Draft

Shalom Patole: Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization

Grace Rebekah: Formal analysis, Software

Elanthenral Sigamani: Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization

Marie Therese Manipadam: Methodology, Formal analysis, Investigation, Writing - Review & Editing

Anish Jacob Cherian: Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization

Deepak Thomas Abraham: Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization

Paul M J: Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization

Rajesh Balakrishnan: Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization

Patricia Sebastian: Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization

Selvamani Backianathan: Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization

Raju Titus Chacko: Writing - Review & Editing, Supervision, Project administration, Funding

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Table 1 Baseline characteristics

Characteristic	Number	%
Female	116	100
Age in years (Median, range)	44.5, 22-67	-
Menopausal status
Premenopausal	76	66.4
Postmenopausal	40	33.6
Performance status^*
ECOG 0	82	70.7
ECOG 1	33	28.4
ECOG 2	1	0.9
T stage(clinical)^*
Tx	9	7.8
T0	1	0.9
T1	4	3.4
T2	44	37.9
T3	27	23.3
T4a	1	0.9
T4b	28	24.1
T4c	1	0.9
T4d	1	0.9
N stage(clinical)^*
N0	27	23.3
N1	65	56.0
N2a	18	15.5
N3a	2	1.7
N3b	1	0.9
N3c	3	2.6
AJCC stage^*
IA	3	2.8
IIA	13	12.1
IIB	31	29.0
IIIA	24	22.4
IIIB	29	27.1
IIIC	7	6.5
Grade of tumour
Grade 1	1	0.9
Grade 2	34	29.3
Grade 3	77	66.4
Unclear/unknown	4	3.4
HER2 expression^*
HER2 negative(IHC score 0)	92	87.6
HER2 low(IHC score 1/2, ISH neg)	13	12.4
Histopathology of tumour
Ductal carcinoma	108	93.1
Metaplastic carcinoma	2	1.7
Apocrine carcinoma	1	0.9
Papillary carcinoma	1	0.9
Unclear/unknown	4	3.4
Type of surgery^*
Breast conservation	15	13.4
Mastectomy	97	86.6
Received adjuvant RT	105	90.5
Received adjuvant capecitabine^*
Overall(N=116)	40	34.5
Without pCR(N=47)	34	72.3

*N varies with missing data for each characteristic

Table 2 Pathological response

Patient subroup	N	%
pCR(ypT0/is N0) overall(N=105)	58	55.2
pCR(ypT0/is, N0) by clinical stage
Stage I/II(N=45)	28	62.2
Stage III (N=57)	27	47.4
Breast pCR(ypT0/is N0/+) (N=104)	63	60.5
Nodal pCR(ypN0) (N=81)	65	80.2
Miller Payne response(N=104)
Miller Payne grade 1	2	1.9
Miller Payne grade 2	6	5.8
Miller Payne grade 3	17	16.3
Miller Payne grade 4	16	15.4
Miller Payne grade 5	63	60.6
Pathological response by grade(N=101)
Grade 1/2(N=31)	15	48.4
Grade 3(N=70)	40	57.1
Pathological response by HER2 expression(N=105)
HER2 negative(IHC score 0) (N=92)	53	57.6
HER2 low(IHC score 1/2, ISH neg) (N=13)	5	38.5

Table 3 Factors associated with pCR (univariate and multivariate)

Characteristic

pCR

No pCR

OR (95% C.I)

P-value

Multivariate p-value*

Age

48 or less

49 or more

40(53.3%)

18(60%)

35(46.7%)

12(40%)

1.31(0.56-3.10)

0.535

-

Menopause

Pre

Post

36(52.9%)

22(59.5%)

32(47.1%)

15(40.5%)

1.30(.58-2.93)

0.521

-

Histology

Others

Ductal carcinoma

4(66.7%)

53(54.6%)

2(33.3%)

44(45.4%)

1.66(0.29-9.49)

0.689

-

Grade of tumor

Grade 3

Grade 1/2

40(57.1%)

15(48.4%)

30(42.9%)

16(51.6%)

1.42(0.61-3.32)

0.415

-

HER2 expression

Negative

Low (1+/2+ ISH neg)

53(57.6%)

5(38.5%)

39(42.4%)

8(61.5%)

0.46(0.14-1.51)

0.158

0.203

T clinical

T3/T4

T2 and below

26(48.1%)

29(60.4%)

28(51.9%)

19(39.6%)

0.61(0.28-0.34)

0.215

-

N stage clinical

N2/3

N0/1

9(42.9%)

49(58.3%)

12(57.1%)

35(41.7%)

0.54(0.20-1.41)

0.202

-

AJCC Stage

Locally advanced (III)

Early(I/II)

27(47.4%)

28(62.2%)

30(52.6%)

17(37.8%)

0.55(0.25-1.21)

0.135

0.144

Neutropenia grade 3/4

Yes

No

15(75%)

43(50.6%)

5(25%)

42(49.4%)

2.93(0.98-8.78)

0.040

0.047

Thrombocytopenia grade 3/4

Yes

No

7(70%)

50(52.6%)

3(30%)

45(47.4%)

2.01(0.49-8.26)

0.260

0.514

Anemia grade 3/4

Yes

No

23(54.8%)

35(55.6%)

19(45.2%)

28(44.4%)

0.97(0.44-2.12)

0.936

0.617

Blood transfusion

Yes

No

25(59.5%)

33(52.4%)

17(40.5%)

30(47.6%)

1.34(0.61-2.95)

0.471

-

*Multivariate binary logistic regression model

Table 4. Adverse events

Adverse event	Grade 1/2 N(%)	Grade 3 N(%)	Grade 4 N(%)
Anemia	72(62.1%)	44(37.9%)	-
Thrombocytopenia	64(55.2%)	8(6.9%)	2(1.7%)
Neutropenia	22(18.9%)	7(6%)	12(10.3%)
Febrile neutropenia	-	4(3.4%)	1(0.9%)
Acute kidney injury	9(7.8%)	-	-
Nausea and vomiting	27(23.3%)	3(2.6%)	-
Myalgia	9(7.7%)	1(0.9%)	-
Peripheral neuropathy	7(6%)	1(0.9%)	-

Preoperative dose-dense docetaxel and cyclophosphamide alternating with epirubicin and cisplatin(ddDCEP): an effective, novel way of incorporating platinum in the treatment of early TNBC

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Abstract

Purpose

Methods

Results

Conclusion

Figures

Highlights

Introduction

Materials And Methods

Statistical analysis

Results

Patient characteristics

Outcomes

Adverse events

Discussion

Conclusion

Declarations

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Data Availability

Funding

Ethics approval

Consent to participate

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Author Contributions

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Status:

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