Preoperative systemic therapy for invasive breast cancer.
In patients undergoing preoperative systemic therapy, indications for radiotherapy and treatment fields should be based on the highest pre-treatment clinical stage, pathological grade, and tumor characteristics.
Preoperative/adjuvant treatment options
HER2-negative disease regimens
Preferred regimen.
*Dose dense AC (adriamycin/cyclophosphamide) sequential paclitaxel once every 2 weeks
*Dose dense AC (adriamycin/cyclophosphamide) sequential paclitaxel once a week
*TC (docetaxel and cyclophosphamide)
Other regimens.
*Dose-dense AC (adriamycin/cyclophosphamide)
*AC (adriamycin/cyclophosphamide) q3w (grade 2B)
* CMF (cyclophosphamide/methotrexate/fluorouracil)
*AC sequential docetaxel q3w
*AC sequential weekly paclitaxel regimen
* EC (epi-adriamycin/cyclophosphamide)
*FEC/CEF sequential T (fluorouracil/epirubicin/cyclophosphamide sequential docetaxel) or (fluorouracil/epirubicin/cyclophosphamide sequential weekly paclitaxel)
* FAC sequential T (fluorouracil/epirubicin/cyclophosphamide sequential 1 paclitaxel per week)
*TAC (docetaxel/adriamycin/cyclophosphamide)
HER2-positive disease regimen
Preferred regimen.
* TAC sequential T + trastuzumab ± pertuzumab (adriamycin/cyclophosphamide sequential paclitaxel plus trastuzumab ± pertuzumab, various schedules)
* TCH (docetaxel/carboplatin/trastuzumab) ± patuximab
Other regimens.
*AC sequential docetaxel + trastuzumab ± patuximab
*Docetaxel + cyclophosphamide + trastuzumab
*FEC sequential docetaxel + trastuzumab + pertuzumab
*FEC sequential paclitaxel + trastuzumab + patuximab
*Paclitaxel + trastuzumab
*Pattuzumab + trastuzumab + docetaxel sequential FEC
*Pattuzumab + trastuzumab + paclitaxel sequential FEC
Retrospective evidence suggests that anthracycline antibiotic-based chemotherapy regimens may be superior to non-anthracycline antibiotic-based regimens in patients with HER2-positive tumors.
Randomized clinical trials have demonstrated improved prognosis with the addition of a paclitaxel to anthracycline antibiotic-based chemotherapy.
CMF and radiotherapy can be given together or CMF can be given first. all other chemotherapy regimens should be given prior to radiotherapy.
Chemotherapy and endocrine therapy as adjuvant therapy endocrine therapy should be given sequentially after chemotherapy.
The listed regimens for HER2-negative disease are all Category 1 when used in an adjuvant setting (except where indicated).
In HER2-positive breast cancer patients with positive axillary lymph nodes, trastuzumab should be added to adjuvant therapy (Class 1).
Trastuzumab should also be considered in patients with HER2-positive lymph node-negative tumors ≥1 cm (Class 1).
Trastuzumab given concurrently with paclitaxel as part of an AC sequential paclitaxel regimen should be optimal and the total duration of dosing should be 1 year.
A patuximab-containing regimen can be given preoperatively to patients with early-stage breast cancer ≥T2 or ≥N1 and HER2-positive. Patients who have not received a patuximab-containing regimen may receive adjuvant patuximab therapy.
Trastuzumab in combination with anthracycline antibiotics is associated with significant cardiotoxicity. Concomitant use of trastuzumab and patuximab with an anthracycline antibiotic should be avoided.
Paclitaxel + trastuzumab may be considered for patients with low-risk stage I, HER2-positive disease, especially those for whom other standard adjuvant regimens are not appropriate due to coexisting disease.
Co-administration schedule for HER2-negative disease: preferred regimen
Dose dense AC sequential paclitaxel chemotherapy
*Adriamycin 60mg/O iv d1
*cyclophosphamide 600mg/O iv d1
Q14d x 4.
(All cycles are accompanied by myeloid growth factor support)
Sequence.
*Paclitaxel 175mg/O iv d1 for 3h d1
Q14d×4.
(All cycles are accompanied by myeloid growth factor support)
Dose dense AC sequential weekly paclitaxel regimen chemotherapy 1
*Adriamycin 60mg/O iv d1
*cyclophosphamide 600mg/O iv d1
Q14d x 4.
(All cycles are accompanied by myeloid growth factor support)
Sequence.
*Paclitaxel 80mg/O iv d1 h qw×12.
TC Chemotherapy.
*Docetaxel 75mg/O IV d1
*Cyclophosphamide 600mg/O iv d1
Q21d×4.
(All cycles were accompanied by bone marrow growth factor support)
The selection, dosing and administration of anticancer drugs and the management of associated toxicities are complex. Adjustment of drug doses and regimens and initiation of supportive therapy interventions are often necessary because of expected toxicities as well as individual patient variability, prior therapy, and coexisting disease. Optimal implementation of anticancer drugs in cancer patients therefore requires a healthcare team with experience in the use of anticancer drugs and the management of associated toxicities.
Combination dosing programs for HER2-negative disease: other options
Dose dense AC chemotherapy
*Adriamycin 60mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q14d x 4.
(All cycles are accompanied by myeloid growth factor support)
AC chemotherapy
*Adriamycin 60mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d x 4.
TAC chemotherapy
*Docetaxel 75mg/O iv d1
*Adriamycin 50mg/O iv d1
*Cyclophosphamide 500mg/O iv d1
Q21d x 6.
(All cycles are accompanied by myeloid growth factor support)
CMF chemotherapy
*Cyclophosphamide 100mg/O orally d1-14
*Methotrexate 40mg/O iv d1, 8
*5-fluorouracil 600mg/O iv d1, 8
Q28d x 6.
AC sequential docetaxel chemotherapy
*Adriamycin 60mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d×4.
Sequential.
*docetaxel 100mg/O iv d1
Q21d x 4.
AC Sequential weekly paclitaxel regimen
*Adriamycin 60mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d x 4.
Sequential.
*paclitaxel 80mg/O iv d1 h qw×12.
EC Chemotherapy.
*Epirubicin 100mg/O iv d1
*cyclophosphamide 830mg/O iv d1
Q21d×8.
FEC sequential docetaxel chemotherapy
*5-fluorouracil 500mg/O iv d1
*Epirubicin 100mg/O iv d1
*Cyclophosphamide 500mg/O iv d1
Q21d x 3.
Sequence.
*docetaxel 100mg/O iv d1
Q21d×3.
FEC sequential 1 paclitaxel weekly
*5-fluorouracil 600mg/O iv d1
*epi-adriamycin 90mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d x 4.
Sequence.
Paclitaxel 100mg/O IV infusion qw×8
FAC sequential 1 paclitaxel weekly
*5-fluorouracil 500mg/O iv d1, 8 or d1, 4
*Adriamycin 50mg/O iv d1
(or CIV 72h)
*Cyclophosphamide 500mg/O iv d1
Q21d x 4.
Sequence.
*Paclitaxel 80mg/O iv d1 h qw×12.
Co-dosing regimen for HER2-positive disease: preferred regimen
AC to T in combination with trastuzumab
*Adriamycin 60mg/O iv d1
*cyclophosphamide 600mg/O iv d1
Q21d×4.
Sequence.
Paclitaxel 80mg/O iv d1 h qw×12
Combination.
*trastuzumab 4mg/kg IV plus first dose of paclitaxel
Sequential.
*trastuzumab 2mg/kg iv qw until completion of 1 year of therapy. As an alternative, trastuzumab 6mg/kg iv q21d can be used after the end of paclitaxel and completion of 1 year of trastuzumab therapy.
Left ventricular ejection fraction (LVEF) was assessed before and during treatment.
AC to T combination trastuzumab + pertuzumab
*Adriamycin 60mg/O iv d1
*cyclophosphamide 600mg/O iv d1
Q21d x 4.
Sequence.
*Pattuzumab 840mg IV d1 then 420mg IV
*Trastuzumab 8mg/kg IV d1 then 6mg/kg IV
*Paclitaxel 80mg/O iv d1, 8, 15
Q21d×4
*Trastuzumab 6mg/kg IV d1
Repeat every 21 days until completion of 1 year of trastuzumab treatment
LVEF assessed before and during treatment.
Dose dense AC sequential paclitaxel combined with trastuzumab
TCH chemotherapy + pertuzumab
*Trastuzumab 8mg/kg IV d1 then 6mg/kg IV
*Pattuzumab 840mg IV d1 then 420mg IV
*Adriamycin 60mg/O iv d1
*Docetaxel 75mg/O IV d1
*Cyclophosphamide 600mg/O iv d1
*Carboplatin AUC 6 IV d1
Q14d×4.
Q21d×6
Sequence.
*Paclitaxel 175mg/O IV d1 for 3h d1
Q14d×4.
Combination.
*trastuzumab 4mg/kg IV plus first dose of paclitaxel
Sequential.
*trastuzumab 2mg/kg iv qw until completion of 1 year of therapy.
As an alternative, trastuzumab 6mg/kg iv q21d can be used after the end of paclitaxel and completion of 1 year of trastuzumab therapy.
LVEF is assessed before and during treatment.
TCH chemotherapy
*Docetaxel 75mg/O IV d1
*Carboplatin AUC 6 IV d1
Q21d x 6
Combination.
*trastuzumab 4mg/kg iv Week 1
Sequential.
*trastuzumab 2mg/kg IV for 17 weeks
Sequential.
*trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
or
*trastuzumab 8mg/kg iv week 1
Sequence.
*trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
Assess LVEF before and during treatment.
*Trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
Assess LVEF prior to and during treatment.
*The optimal frequency of LVEF assessment during adjuvant trastuzumab therapy is not known.
The FDA labeling recommendation is to measure LVEF prior to trastuzumab initiation and every 3 months during treatment.
The selection, dosing and administration of anticancer drugs and the management of associated toxicities are complex. Adjustment of drug doses and regimens and initiation of supportive therapy interventions are often necessary because of anticipated toxicities as well as individual patient variability, prior therapy, and coexisting disease. Optimal implementation of anticancer drugs in cancer patients therefore requires a healthcare team with experience in the use of anticancer drugs and the management of associated toxicities.
Combination dosing regimens for HER2-positive disease: other regimens
AC sequential docetaxel chemotherapy in combination with trastuzumab
*Adriamycin 60mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d×4
Sequential.
*docetaxel 100mg/O iv d1
Q21d×4
Combination.
*trastuzumab 4mg/kg iv week 1
Sequence.
*trastuzumab 2mg/kg iv qw×11
Sequential.
*trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
LVEF was assessed before and during treatment.
AC sequential docetaxel chemotherapy combined with trastuzumab and pertuzumab
*Adriamycin 60mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d×4
Sequence.
*Pattuzumab 840mg IV d1 then 420mg IV
*Trastuzumab 8mg/kg IV d1 then 6mg/kg IV
*Docetaxel 75-100mg/O iv d1
Q21d×4
Sequence.
*trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
LVEF assessed before and during treatment.
Docetaxel/cyclophosphamide chemotherapy in combination with trastuzumab
*Docetaxel 75mg/O IV d1
*Cyclophosphamide 600mg/O iv d1
Q21d x 4
Combination.
Trastuzumab 4mg/kg iv week 1
Then.
Trastuzumab 2mg/kg iv qw×11
Then.
Trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
or
*trastuzumab 8mg/kg iv week 1
Sequence.
*trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
LVEF was assessed before and during treatment.
FEC chemotherapy sequential pertuzumab + trastuzumab + docetaxel
*5-fluorouracil 500mg/O iv d1
*Epirubicin 100mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d×3
Sequence.
*Pattuzumab 840mg IV d1 then 420mg IV
*Trastuzumab 8mg/kg IV d1 then 6mg/kg IV
*Docetaxel 75-100mg/O iv d1
Q21d×3
Sequence.
*trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
Assess LVEF before and during treatment.
*The optimal frequency of LVEF assessment during adjuvant trastuzumab therapy is not known.
The FDA labeled recommendation is to measure LVEF prior to trastuzumab initiation and every 3 months during treatment.
FEC chemotherapy sequential pertuzumab + trastuzumab + paclitaxel
*5-fluorouracil 500mg/O iv d1
*Epirubicin 100mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d×3
Sequence.
*Pattuzumab 840mg IV d1 then 420mg IV
*Trastuzumab 8mg/kg IV d1 then 6mg/kg IV
*Paclitaxel 80mg/O iv d1, 8, 15
Q21d×3
Sequence.
*trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
LVEF was assessed before and during treatment.
Paclitaxel + trastuzumab
*Paclitaxel 80mg/O IV qw x 12
Combination.
*trastuzumab 4mg/kg IV plus first dose of paclitaxel
Sequential.
*trastuzumab 2mg/kg iv qw until completion of 1 year of therapy. As an alternative, trastuzumab 6mg/kg iv q21d can be used after the end of paclitaxel and completion of 1 year of trastuzumab therapy.
LVEF was assessed before and during treatment.
Paltuzumab + trastuzumab + docetaxel sequential FEC chemotherapy
Neoadjuvant therapy.
*Pattuzumab 840mg IV d1 then 420mg IV
*trastuzumab 8mg/kg IV d1 then 6mg/kg IV
*Docetaxel 75-100mg/O iv d1
Q21d×4
Then adjuvant therapy
*5-Fluorouracil 600mg/O iv d1
*epi-adriamycin 90mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d×3
Sequence.
*trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
LVEF was assessed before and during treatment.
Paltuzumab + trastuzumab + paclitaxel sequential FEC chemotherapy
Neoadjuvant therapy.
*Pattuzumab 840mg IV d1 then 420mg IV
*trastuzumab 8mg/kg IV d1 then 6mg/kg IV
*paclitaxel 80mg/O iv d1, 8, 15
Q21d×4
Then adjuvant therapy
*5-Fluorouracil 600mg/O iv d1
*epi-adriamycin 90mg/O iv d1
*Cyclophosphamide 600mg/O iv d1
Q21d×3
Sequence.
*trastuzumab 6mg/kg iv q21d until completion of 1 year of trastuzumab therapy
Assess LVEF before and during treatment.
*The optimal frequency of LVEF assessment during adjuvant trastuzumab therapy is unknown. the FDA labeling recommendation is to measure LVEF prior to trastuzumab initiation and every 3 months during treatment.