Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Carcinoma, Ductal, Breast

Inflammatory Breast Neoplasms

Carcinoma

Carcinoma, Ductal

Breast Diseases

Skin Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Inflammatory Breast Cancer

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Paclitaxel

Cyclophosphamide

Albumin-Bound Paclitaxel

Epirubicin

Pertuzumab

Tubulin Modulators

Antimitotic Agents

nab-Paclitaxel (125 mg/m² weekly, infusion) is applicated for 12 weeks, followed by epirubicin and cyclophosphamide, applicated 4 cycles 3-weekly . In case of HER2-positive tumor patients receive tarstuzumab and pertuzumab 3-weekly during all cycles.

Paclitaxel (80 mg/m² weekly, infusion) is applicated for 12 weeks, followed by epirubicin and cyclophosphamide, applicated 4 cycles 3-weekly . In case of HER2-positive tumor patients receive tarstuzumab and pertuzumab 3-weekly during all cycles.

nab-Paclitaxel 125 mg/m² weekly for 12 weeks

nab-Paclitaxel

Michael Untch, Prof MD

Current guidelines as those from the AGO-Breast commission recommend for neoadjuvant breast cancer patients either a sequence of 4 cycles EC followed by 4 cycles of a taxane or 6 cycles of TAC based on previous large scale studies.

Treatment of patients with HER2-positive disease should include also simultaneous application of trastuzumab.

Solvent-based taxanes (paclitaxel, docetaxel) cause severe toxicities not only by the active agents itself but also by the solvents like cremophor. Nab-paclitaxel (Abraxane®) is a solvent-free formulation of paclitaxel encapsulated in albumin. It does not require premedication with corticosteroids or antihistamines to prevent the risk of solvent-mediated hypersensitivity reactions. This new formulation improves safety profile, allows higher dosing with shorter infusion duration, and produces higher tumor drug concentration.

As neoadjuvant treatment does not only allow to compare competing treatment approaches with a very high quality (homogenous treatment population, precise assessment of response by histological assessment), but also to identify predictive markers, this trial will compare weekly nab-paclitaxel with solvent-based paclitaxel at their currently optimal doses.

In case of HER2-positive tumor status patients receive Pertuzumab and Trastuzumab additionally.

Primary Objectives:

To compare the pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable or locally advanced primary breast cancer

Secondary Objectives:

* To assess the pCR rates per arm separately for the stratified subpopulations.
* To determine the rates of ypT0/is ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0; and regression grades.
* To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in both arms.
* To assess clinical response rate after taxane in both groups
* To determine the breast conservation rate after each treatment.
* To assess the toxicity and compliance.
* To assess the time of onset of grade 3 neuropathy
* To assess the time of resolution of grade 3/4 neuropathy to at least grade 1
* To determine loco-regional invasive recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), and overall survival (OS) in both arms and according to stratified subpopulations.
* To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative at surgery and treated with sentinel node biopsy alone.
* To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery.
* To examine and compare pre-specified molecular markers such as SPARC, gp60, calveoline 1 and other markers potentially differentially predicting efficacy of nab-paclitaxel and solvent-based paclitaxel on core biopsies before, during and after chemotherapy.

Objectives of Substudies:

* To assess, characterize, and correlate circulating tumor cells and proteins with the effect of treatment (CTC Substudy).
* To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated toxicity and histologically assessed treatment effect (Pharmacogenetic substudy)
* To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, LH , Anti-Müller Hormone, ultrasound-follicle count in patients aged \< 45 years.

Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

A Randomized Phase III Trial Comparing Nanoparticle-based Paclitaxel With Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Patients With Early Breast Cancer (GeparSepto)

No microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast and axilla.

Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries.

The primary endpoint will be summarized as pathological complete remission rate for each treatment group.

Response (by physical examination, imaging response, breast conservation) will also be summarized as rates in each treatment group.

To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in both arms.

Descriptive statistics for the 4 treatments (each taxane +/- anti-HER2-treatment) will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.

To assess clinical response rate after taxane in both groups.

To determine the breast conservation rate after each treatment.

To assess the time of onset of grade 3 neuropathy.

To assess the time of resolution of grade 3/4 neuropathy to at least grade 1.

To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative at surgery and treated with sentinel node biopsy alone.

To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery.

To examine and compare pre-specified molecular markers such as SPARC, gp60, calveoline 1 and other markers potentially differentially predicting efficacy of nab-paclitaxel and solvent-based paclitaxel on core biopsies before, during and after chemotherapy.

The aim is to identify potential predictive short and long term parameters.

To assess, characterize, and correlate circulating tumor cells and proteins with the effect of treatment.

To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated toxicity and histologically assessed treatment effect.

To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, LH , Anti-Müller Hormone, ultrasound-follicle count in patients aged \<45 years.

LRRFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

DDFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

IDFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

OS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

If it can be shown at an interim analysis that the positive predictive value for a pCR of a negative (\>=3) core biopsies before surgery in patients with complete clinical response is \>90%, these patients might opt for having no further breast surgery.

Celgene Corporation

Roche Pharma AG

German Breast Group

Anti-Infective Agents

Trastuzumab

Carboplatin

Doxorubicin

Liposomal doxorubicin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

PM(Cb):

paclitaxel 80mg/m² 18 times weekly simultaneously with NPLD (Myocet®)20mg/m² 18 times weekly simultaneously with carboplatin AUC 1.5 18 times weekly (only in patients with TNBC) Patients with HER2-positive disease will receive trastuzumab 6 (8) mg/kg every 3 weeks and pertuzumab 420 (840) mg every 3 weeks simultaneously to all cycles.

ETC:

epirubicin 150mg/m² every 2 weeks for 3 cycles followed by paclitaxel 225 mg/m² every 2 weeks for 3 cycles followed cyclophosphamide 2000 mg/m² every 2 weeks for 3 cycles. Patients with HER2-positive disease will receive trastuzumab 6 (8) mg/kg every 3 weeks and pertuzumab 420 (840) mg every 3 weeks simultaneously to all T and C cycles.

non-pegylated liposomal doxorubicin

Carboplatin AUC 1.5 18 times weekly (only in patients with triple-negative breast cancer).

420 (840) mg every 3 weeks simultaneously to all T and C cycles in the ETC arm and to all cycles in the PM(Cb) arm.

Trastuzumab 6 (8) mg/kg every 3 weeks simultaneously to all T and C cycles in the ETC arm and to all cycles in the PM(Cb) arm.

after first anemia grade ≥2 and in case of randomisation: Ferric carboxymaltose i.V. 1000 mg followed 1 week later by an injection of ferric carboxymaltose i.V. 500 mg (if body weight is \<70 kg) or 1000 mg (if body weight is ≥70 kg). In case body weight is \<50 kg, both dosages will be reduced to 500 mg each.

Ferric carboxymaltose

Andreas Schneeweiss, MD, Prof.

Two regimen are currently considered to have highest efficacy for patients with high-risk early stage breast cancer: sequential treatment of high dose epirubicin, taxane, and cyclophosphamide concomitantly with a dual HER2-blockade, and weekly treatment with paclitaxel/non-pegylated liposomal doxorubicin with dual HER2-blockade or carboplatin. The aim of the GeparOcto study is to compare those two regimen/strategies.

Both regimens are myelosuppressive with a significant incidence of chemotherapy induced anaemia.

The second aim of the GeparOcto study is therefore to compare the use of parental ferric carboxymaltose versus physician's choice for the treatment of chemotherapy-induced anemia in patients with iron deficiency.

Several recent strategies have improved efficacy of systemic treatment for patients with high-risk early stage breast cancer: the addition of a dual HER2-blockade for HER2-positive; the implementation of carboplatin for TNBC and the use of dose-dense or dose-dense, dose escalated chemotherapy in all high-risk subtypes of breast cancer. Two regimen are currently considered to have highest efficacy: sequential treatment of high dose epirubicin, taxane, and cyclophosphamide (ETC) concomitantly with a dual HER2-blockade mainly based on the AGO ETC adjuvant study, and weekly treatment with paclitaxel/non-pegylated liposomal doxorubicin with dual HER2-blockade or carboplatin (PM(Cb)) based on the GeparSixto study. The aim of the GeparOcto study is to compare those two regimen/strategies.

Both regimens are myelosuppressive with a significant incidence of chemotherapy induced anaemia. Anemia is often associated with impaired physical and cognitive function and consequently the patients suffer from a reduced quality of life. Surgical complications are higher in anemic patients. The second aim of the GeparOcto study is therefore to compare the use of parental ferric carboxymaltose versus physician's choice for the treatment of chemotherapy-induced anemia in patients with iron deficiency.

A Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)

A Randomized Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)

To compare the pathological complete response (pCR= ypT0/is ypN0) rates of neoadjuvant treatment with sequential, dose-dense, dose-intensified ETC(+HP) vs. weekly PM(Cb)(+HP) in patients with high-risk operable or locally advanced breast cancer.

Masked role for assessor.

Only for those patients randomized for the supportive anemia treatment:

To compare the frequency of patients reaching hemoglobin (Hb) levels ≥ 11g/dl 6 weeks after treatment start of a first episode of anemia grade ≥2 (Hb \< 10g/dl) between patients receiving supportive treatment for iron deficiency with parental ferric carboxymaltose versus physician's choice (no supportive treatment, oral iron substitution, erythropoiesis-stimulating agent (ESA), or both).

To assess the pCR rates per arm separately for the stratified subpopulations.

Response (by physical examination, imaging response, breast conservation) will also be summarized as rates in each treatment group).

Descriptive statistics for the 5 treatments (ETC +/- anti-HER2-treatment, PM +/- anti-HER2-treatment, PMCb) will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.

To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative (ypN0) at surgery and treated with sentinel node biopsy alone.

To correlate response (complete vs. partial vs. no change) measured by best appropriate imaging method after 6 weeks of treatment with pCR.

To examine and compare pre-specified molecular and histological markers such as Ki67, stromal TILs, immunologically relevant genes (e.g. CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21, IDO1, PD-1, PDL1, CTLA4, FOXP3, and combinations of these genes) as well as e.g. CD138, CD47, MET and other markers on core biopsies before and eventually also on surgical tissue after end of chemotherapy.

The aim is to identify potential predictive short and long term parameters.

To examine PIK3CA mutation in patients with HER2-positive tumor on core biopsies.

To compare quality of life using the FACT-An anemia and fatigue questionnaire between the supportive treatment arms.

To compare the median time to achieve a hemoglobin level ≥11g/dl between the supportive treatment arms.

To compare the frequency of patients with hemoglobin level ≥11g/dl in the week after the end of the last chemotherapy cycle between the supportive treatment arms.

To demonstrate that PET-CT before surgery in addition to conventional presurgical staging methods can decrease the mastectomy rate in patients receiving neoadjuvant chemotherapy for breast cancer.

Amgen

Teva Pharmaceuticals USA

Vifor Pharma

Amino Acids

Bevacizumab

Lapatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Carboplatin AUC 2 min/mL weekly, infusion will be used as Add-on to the background therapy (same as comparator arm)

background treatment with NLPD (Myocet), Paclitaxel, Herceptin (Trastuzumab fpr Her2 pos), Tyverb (Lapatinib for Her2 pos), Avastin (Bevacizumab for triple negative) agents are used according to marketed formulation via normal procedures at each site and applied according to recommendations of the manufacturers.

Carboplatin, AUC, 2 min/mL weekly, infusion

background treatment according to standards fpr triple negative and Her2pos breast cancer patients Paclitaxel: 80 mg/m² i.v. given weekly on day 1 q day 8 for 18 weeks. NPLD (Myocet®): 20 mg/m² weekly on day 1 q day 8 for 18 weeks Trastuzumab (only for HER2-positive patients): Loading dose: 8 mg/kg, Maintenance dose: 6 mg/kg, day 1 q day 22 for 6 cycles. Post-surgery: up to a total duration of 1 year according to current AGO guidelines Lapatinib 750 mg/day p.o. continuously for 18 weeks; in case of good tolerability (no CTC grade II toxicity except alopecia and nausea/vomiting) during the first cycle the dose may be escalated to 1000 mg.

Bevacizumab: 15 mg/kg i.v., day 1 q day 22 for 6 cycles (only in TNBC patients).

background treatment

Gunter von Minckwitz, MD, Prof

Study participants with primary breast cancer will receive a standard chemotherapy with an anthracycline and a taxane as well as trastuzumab in case of HER2-positive tumors at doses and duration in concordance to current treatment guidelines. Patients will be receive and benefit in addition currently not in the neoadjuvant setting registered medication as lapatinib or bevacizumab of which significant increases of cure (pCR) rates have been reported in previous phase III studies. Patients randomized to carboplatin will receive in addition to the described backbone therapies a potentially active agent which suggested synergy of efficacy with chemotherapies as well as targeted agents. Patients might have the risk of an increase in toxicities due to the added agents and will have additional burden due to investigations required for study participation. However, due to the severity of the underlying disease and the high risk of relapse and death due to the stage of disease, this increase in toxicity and burden appears less relevant compared to the potential higher efficacy and finally cure rate by the incorporated treatments.

Anthracycline/taxane based combination chemotherapy of at least 18 weeks represents the standard of care in the neoadjuvant setting. In HER2-positive disease trastuzumab is given simultaneously to chemotherapy. Recent data from the Neo-Altto and Neosphere trials suggest that a dual blockage of the HER2 receptor with e.g. trastuzumab and lapatinib reach significantly higher pCR rates than trastuzumab alone and should therefore represent the treatment back-bone of new neoadjuvant trials. A preplanned subgroup analysis of the GeparQuinto study demonstrated that in TNBC the addition of bevacizumab resulted in a significant increase of pCR rates (HR 1.4).

Having a better cardiac tolerability profile compared to conventional anthracyclines, the non-pegylated liposomal encapsulated doxorubicin (NPLD) Myocet® might provide the possibility to combine taxane, anthracycline, platinum salt as well with targeted agents as double HER2 blockage or bevacizumab.

Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer

A Randomized Phase II Trial Investigating the Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer

Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries. Surgery takes place shortly after the 18 weeks (six 3-week cycles) chemotherapy treatment. No microscopic evidence of residual viable tumor cells in all resected specimens of the breast and axilla meets the primary endpoint.

To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests. (sonography, mammography, or MRI) after treatment in both arms.

LRRFS, RRFS, LRFS, DDFS, IDFS and OS are defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

Tolerability and Safety: Descriptive statistics for the 4 treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped

• To assess the pCR rates per arm separately in patients with triple-negative tumors and HER2-positive tumors.

To determine the breast and axilla conservation rate after each treatment.

To assess the pCR rate in patients with a clinical complete response and a negative core biopsy before surgery.

To examine and compare pre-specified molecular markers such as BRCA1-mRNA, P53, ALDH1, p4E-BP1, IL-8 metagene, B-Cell metagene as well as exploratory analyses and lymphocyte infiltration on core biopsies before and surgical tissue after end of chemotherapy. The aim is to identify potential predictive short and long term parameters.

To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, Anti-Müller Hormone, ultrasound-follicle count in patients aged \<45 years.

GlaxoSmithKline

Bone Density Conservation Agents

Antibodies

Immunoglobulins

Denosumab

nab-Paclitaxel weekly for 12 weeks. Patients with HER2-positive tumors receive Trastuzumab and Pertuzumab. Patients with triple-negative tumors receive Carboplatin in parallel to nab-paclitaxel.

nab-Paclitaxel day 1,8 q22 for 12 weeks. Patients with HER2-positive tumors receive Trastuzumab and Pertuzumab. Patients with triple-negative tumors receive Carboplatin weekly in parallel to nab-paclitaxel.

Epirubicin and Cyclophosphamide 600mg/m² for 4 times. Patients with HER2-positive tumors receive Trastuzumab and Pertuzumab.

Denosumab 120 mg every 4 weeks for 6 cycles

nab-paclitaxel 125 mg/m² weekly for 12 weeks or at day 1,8 q22 for 4 cycles (12 weeks)

Epirubicin 90 mg/m² every 2 or 3 weeks for 4 times

Cyclophosphamide 600 mg/m² every 2 or 3 weeks for 4 times

Carboplatin AUC 2 weekly in parallel to nab-Paclitaxel

Trastuzumab 6 (8) mg/kg every 3 weeks simultaneously to all chemotherapy cycles

Pertuzumab 420 (840) mg every 3 weeks simultaneously to all chemotherapy cycles

Jens Uwe Blohmer, MD

Pharmacologic inhibition of RANKL attenuates the development of mammary carcinoma and inhibits metastatic progression in multiple mouse models.

In a retrospective analysis it could be demonstrated that elevated expression of RANK was found in 14.5% of patients overall, with a significant predominance in patients with hormone-receptor-negative disease. Expression of RANK was associated with a higher pathological complete response rate but with a shorter disease-free and overall survival. The ABCSG-18 study showed that adjuvant denosumab reduces clinical fractures, improves bone health, and can be administered without added toxicity.

It appears therefore reasonable to test denosumab, a clinically available antibody against RANKL in patients with hormone-receptor-negative primary breast cancer as an adjunct to neoadjuvant chemotherapy for its ability to increase pCR rate and improve outcome in relation to the expression of RANK.

RANK ligand (RANKL), a key factor for bone remodeling and metastasis, is crucial for the development of mouse mammary glands during pregnancy. RANKL functions as a major paracrine effector of the mitogenic action of progesterone in mouse and human mammary epithelium via its receptor RANK and has a role in ovarian hormone-dependent expansion and regenerative potential of mammary stem cells. Pharmacologic inhibition of RANKL attenuates the development of mammary carcinoma and inhibits metastatic progression in multiple mouse models.

In a retrospective analysis of 601 patients treated in the GeparTrio study with chemotherapy (TAC) it could be demonstrated that elevated expression of RANK (immunohistochemical score \> 8.5 using the N-1H8 antibody by Amgen) was found in 14.5% of patients overall, with a significant predominance in patients with hormone-receptor-negative disease (33.7% vs 6.4% tumors positive for RANK). Expression of RANK was associated with a higher pathological complete response rate (pCR) (23.0% vs 12.6%) but with a shorter disease-free and overall survival. The ABCSG-18 study showed that adjuvant denosumab reduces clinical fractures, improves bone health, and can be administered without added toxicity. Moreover denosumab improves disease-free survival in postmenopausal woman with hormone receptor positive breast cancer.

It appears therefore reasonable to test denosumab, a clinically available antibody against RANKL in patients with hormone-receptor-negative primary breast cancer as an adjunct to neoadjuvant chemotherapy for its ability to increase pCR rate and improve outcome in relation to the expression of RANK.

Denosumab as an add-on Neoadjuvant Treatment (GeparX)

Investigating Denosumab as an add-on Neoadjuvant Treatment for RANK-positive or RANK-negative Primary Breast Cancer and Two Different Nab-Paclitaxel Schedules ; 2x2 Factorial Design (GeparX)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)	NCT01583426	Tubular Breast ... Mucinous Breast... Breast Cancer F... Invasive Ductal... Tubular Breast ... HER-2 Positive ... Inflammatory Br... Inflammatory Br...	nab-Paclitaxel Paclitaxel	18 Years -	German Breast Group
A Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)	NCT02125344	Tubular Breast ... Tubular Breast ... Mucinous Breast... Breast Cancer F... Invasive Ductal... HER2 Positive B... Inflammatory Br...	non-pegylated l... Carboplatin Paclitaxel Epirubicin Cyclophosphamid... Pertuzumab Trastuzumab Ferric carboxym...	18 Years -	German Breast Group
Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer	NCT01426880	Tubular Breast ... Mucinous Breast... Breast Cancer F... Invasive Ductal... Tubular Breast ... HER-2 Positive ... Inflammatory Br... Inflammatory Br...	Carboplatin background trea...	18 Years -	German Breast Group
A Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)	NCT02125344	Tubular Breast ... Tubular Breast ... Mucinous Breast... Breast Cancer F... Invasive Ductal... HER2 Positive B... Inflammatory Br...	non-pegylated l... Carboplatin Paclitaxel Epirubicin Cyclophosphamid... Pertuzumab Trastuzumab Ferric carboxym...	18 Years -	German Breast Group
Denosumab as an add-on Neoadjuvant Treatment (GeparX)	NCT02682693	Breast Cancer F... Tubular Breast ... Mucinous Breast... Invasive Ductal... HER2 Positive B... Inflammatory Br... Tubular Breast ...	Denosumab nab-Paclitaxel Epirubicin Cyclophosphamid... Carboplatin Trastuzumab Pertuzumab	18 Years - 75 Years	German Breast Group

Spots Global Cancer Trial Database for tubular breast cancer stage iii