Ba ckground: Standard adjuvant or neo-adjuvant chemotherapy of primary breast cancers consists of docetaxel and the combination of anthracyclin-c yclophosphamide in two steps. According to international literature , the neo-adjuvant treatment of triple negative tumours by the combination of docetaxel-carboplatin allows a high rate of pathological complete remission and the adjuvant treatment of small, node negative HER2+ tumours by the combination of paclitaxel-trastuzumab allows a negligible recurrence rate together with a very good tolerance. Methods: Our aim was the retrospective analysis of the alternative chemotherapy regimens in our patient population. Results: The neo-adjuvant docetaxel-carboplatin allowed a 55% pathological complete remission rate among 20 patients. With the adjuvant paclitaxel-trastuzumab , we did not notice any recurrence among 5 patients at a median follow - up of 18 months. Conclusion: Our results correspond to the literature data. The spread of the protocols in the clinical practice is proposed.
Localised or regionally advanced invasive breast cancer is curable in 75% of the cases [
The principal aim of the chemotherapy is the eradication of the micro-metastases, present at the time of the diagnosis of the disease, even if undetectable by the staging examinations with other words the lowering of the risk of distant recurrence. Chemotherapy administered after surgery is called adjuvant that before surgery is called neo-adjuvant. In presence of palpable axillary lymph nodes the first element of the multimodal treatment is the neo-adjuvant chemotherapy. In absence of palpable axillary lymph nodes the order of surgery and chemotherapy may be determined relatively freely, taking into account several arguments. It has not been proven that either the adjuvant or the neo-adjuvant application of the chemotherapy could provide any advantage over the other in terms of overall survival [
In case of a proportionately big primary tumour the neo-adjuvant chemotherapy may allow a breast conserving intervention, a sectorectomy rather than a mastectomy [
The most efficacious perioperative chemotherapy regimen is composed of two parts and three drugs. In absence of palpable axillary lymph nodes 3 cycles of docetaxel are followed by 3 cycles of an anthracyclin-cyclophosphamide combination. In presence of palpable axillary lymph nodes the same protocols are given for 4 cycles [
Alternative regimens are proposed by the international literature as well. The neo-adjuvant treatment of triple negative tumours by the combination of docetaxel (75 mg/m2)-carboplatin (AUC 6) allows a high rate of pathological complete remission [
We performed a retrospective analysis of the patients treated with neo-adjuvant docetaxel-carboplatin for a triple negative, at maximum stage T4N3M0 primary breast cancer or with adjuvant paclitaxel-trastuzumab combination for a HER2+, at maximum stage T2aN0M0 primary breast cancer between 01.01.2012. and 31.12.2017. at the Department of Oncoradiology of the Petz Aladár Hospital, Győr, Hungary.
Every patient with a primary breast cancer corresponding to the above phenotypes and stages was eligible for the analysis. The neo-adjuvant docetaxel-carboplatin protocol was administered with a carboplatin dose of AUC 5. The adjuvant paclitaxel-trastuzumab protocol was administered with 4 to 6 cycles of three weekly 175 mg/m2 paclitaxel as compared to the original publications [
The retrospective analysis is part of the auto-evaluation of our clinical practice. We followed validated chemotherapeutic protocols. Therefore we did not submit our study to an ethics committee approval.
For the neo-adjuvant protocol the primary outcome was the rate of pathological complete remission, the secondary outcome was the overall survival. For the adjuvant protocol the outcome was the rate of relapse.
We did not use any advanced statistical methods. Rate of pathological complete remission and relapse were calculated as proportions to the whole treated population. The survival data are given case by case in
20 patients were treated with the neo-adjuvant docetaxel-carboplatin protocol (
Regarding long term efficacy, recurrence was noticed in 5 cases. 3 patients were lost after a median follow up of 20 months, 2 patients are still receiving palliative chemotherapy. The recurring tumours were of high risk at the moment of diagnosis (stage cT4 or cN2-3). The median follow up of patients without recurrence is 41 months.
5 patients were treated with the adjuvant paclitaxel-trastuzumab protocol (
The decision making algorithm currently in use at our department is shown in
Overtreatment by surgery and chemotherapy as well has been part of the clinical
Patient | Age | Tumour | Surgery | Rx therapy | Cx therapy | Residual | TTR | OS |
---|---|---|---|---|---|---|---|---|
1 | 39 | cT2N1, G3, mBRCA1 | Mastectomy, ABD | 50 Gy | 6 TXT-CBP | 4 × 2 mm | ? | >7 |
2. | 45 | cT3N1, G3 | Mastectomy, ABD | ? | 6 TXT-CBP | pCR | ? | >7 |
3. | 65 | cT1N2, G3 | Mastectomy, ABD | 12 Gy | 6 TXT-CBP | 62 mm | 1 | 14 |
4. | 38 | cT2N1, G3 | Sectorectomy, ABD | ? | 6 TXT-CBP | pCR | ? | >12 |
5. | 51 | cT2N0, G3 | Sector., sentinel | 50 Gy | 6 TXT-CBP | pCR | ? | >13 |
6. | 63 | cT4N2, G3 | Mastectomy, ABD | 50 Gy | 6 TXT-CBP | 54 mm | 13 | >20 |
7. | 59 | cT3N1, G3 | Mastectomy, ABD | 50 Gy | 6 TXT-CBP | pCR | ? | >18 |
8. | 63 | cT3N1, G3 | Mastectomy, ABD | 50 Gy | 5 TXT-CBP | pCR | ? | >18 |
9. | 53 | cT4N2, G3 | Mastectomy, ABD | 60 Gy | 6 TXT-CBP | pCR | ? | >37 |
10. | 70 | cT1N3, G3 | Sectorectomy, ABD | 50 Gy | 6 TXT-CBP | pCR | ? | >41 |
11. | 77 | cTxN2, G3 | Mastectomy, ABD | 50 Gy | 6 TXT-CBP | pCR | ? | >44 |
12. | 85 | cT4N0, G3 | Mastectomy, ABD | 50 Gy | 2 TXT-CBP | 80 mm | 12 | 17 |
13. | 69 | cT4N3, G2 | Mastectomy, ABD | 50 Gy | 5 TXT-CBP | 90 mm | 12 | 20 |
14. | 55 | cT2N1, G3 | Mastectomy, ABD | ? | 6 TXT-CBP | pCR | ? | >56 |
15. | 41 | cT2N0, G3 | Sector., sentinel | 50 Gy | 6 TXT-CBP | 5 mm | ? | >57 |
16. | 58 | cT4N1, G3 | Mastectomy, ABD | 60 Gy | 6 TXT-CBP | 27 mm | ? | >57 |
17. | 29 | cT2N0, G2 | Sector, sentinel | ? | 6 TXT-CBP | pCR | ? | >65 |
18. | 61 | cT4N1, G3 | Mastectomy, ABD | ? | 6 TXT-CBP | 10 mm IS | 35 | 36 |
19. | 70 | cT2N1, G3 | Sector., sentinel | 50 Gy | 6 TXT-CBP | 3 mm | ? | >67 |
20. | 43 | cT2Nx, G3 | Sectorectomy, ABD | 50 Gy | 6 TXT-CBP | pCR | ? | >68 |
Patient | Age | Tumour | Surgery | Rx therapy | Cx therapy | Residual | TTR | OS |
---|---|---|---|---|---|---|---|---|
1. | 62 | pT2N0, ER- | Mastectomy, ABD | ? | 4 TAX-HER | ? | ? | >12 |
2. | 55 | pT1N1, ER-, DCIS | Sector., sentinel | 50 Gy | 6 TXT-HER | ? | ? | >13 |
3. | 60 | pT2SN0, ER- | Sector., sentinel | 50 Gy | 6 TAX-HER | ? | ? | >18 |
4. | 75 | pT1SN0, ER+, DCIS | Mastectomy, sent. | ? | 3 TAX-HER | ? | ? | >30 |
5. | 55 | Duplex pT2SN0, ER- | Sector., sentinel | 50Gy | 6 TAX-HER | ? | ? | >43 |
Luminal A | Luminal B | HER2+ | Triple negative | |
---|---|---|---|---|
Neo-adjuvant | Hormonal | AC + T | AC + T-HER-(PER) | TXT-CBP |
Adjuvant | AC + T | AC + T | TAX-HER | AC + T |
AC + TH |
practice. The possibility to obtain the same recurrence free rate by less aggressive interventions was first proven in the field of surgery. The Halstead amputations were gradually replaced by simple mastectomy and when possible sectorectomy as well as the axillary block dissections by sentinel techniques and radiotherapy [
The neo-adjuvant docetaxel-carboplatin protocol was originally described with a carboplatin dose of AUC 6 [
The cohort of 20 patients who received the docetaxel-carboplatin combination can be considered as statistically representative. The good pathological complete remission and survival data show the value of the alternative chemotherapy for these tumours of especially unfavourable prognostic (of high grade and refractory to hormone- and growth factor receptor targeted treatment). The cohort of 5 patients who received the paclitaxel-trastuzumab combination is statistically too small. The results are considered as advertising rather than approving. (The protocol does not figure in the Hungarian Textbook for Chemotherapy [
There is no sufficient evidence to support the role of adjuvant radiotherapy in case of pathological complete remission obtained with chemotherapy. Initial tumour extension and nodal involvement may influence the decision [
Trastuzumab can be used in neo-adjuvant setting as well for HER2+ tumours and it allows a high rate of pathological complete remission. The addition of pertuzumab to the combination may further rise the rate of pathological complete remission but it has not been proven to have an impact on the overall survival, thus its systematic use is not proposed [
According to novel results axillary block dissection may be replaced by radiotherapy in cases when only microscopic metastases are found in the sentinel lymph nodes [
Immuno-radiotherapy is subject of investigations. According to some hypotheses the application of neo-adjuvant irradiation and checkpoint inhibition may have a synergetic action by the parallel release of tumour antigens and activation of the immune system [
Dose dense adjuvant chemotherapy is another field of investigation. The density may be raised by the increase of the treatment doses or the decrease of the intervals between two treatments. Both strategies improve the recurrence free rate and the overall survival by some percents on the expense of higher toxicity [
The molecular and immunologic characterisation of triple negative tumours is proposed to yield more specific and hopefully efficacious targeted treatments for this still poor prognostic patient population [
The optimal duration of adjuvant chemotherapy for HER2+ breast cancers is debated. Although the non-inferiority of a 9 months long treatment was not approved in an earlier study [
The main limitation of our study is the relatively small number of patients included. As the original international studies were large trials, they stand for the validity of our results. We believe that the interest of our work is the flexible use of different upcoming literature data that allow a phenotype dependent management of our patients with primary breast cancer. In addition, these protocols are less toxic or more comfortable to schedule as compared to the standard regimens.
The neo-adjuvant docetaxel-carboplatin combination may allow a good rate of pathological complete remission for triple negative breast cancers.
The adjuvant paclitaxel-trastuzumab combination may allow a good recurrence free rate for HER2+, node negative breast cancers of small size.
The authors declare no conflicts of interest regarding the publication of this paper.
Kullmann, T., Agyemang-Prempeh, K., Ambrus, A., Herodek, G., Hillier, B., Kocsis, K., Laszip, I., Mák, M., Pintér, T. and Sipőcz, I. (2019) A Single Centre Experience with Phenotype Dependent Perioperative Chemotherapy for Primary Breast Cancer. Journal of Cancer Therapy, 10, 21-27. https://doi.org/10.4236/jct.2018.101002