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Breast Diseases

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All Drugs and Chemicals

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Antirheumatic Agents

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Doxorubicin

Liposomal doxorubicin

Epirubicin

Antibiotics, Antitubercular

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Alkylating Agents

Antineoplastic Agents, Alkylating

Enzyme Inhibitors

Preoperative Anthracycline Doxorubicin 60mg/m2 (or Epirubicin 100 mg/m2) + Standard of Care chemotherapy and drugs + Thermotherapy. Thermotherapy at first 3 chemotherapy treatments for Anthracycline chemotherapy nominally every 21±7 days plus Standard of Care chemotherapy.

Preoperative Anthracycline Doxorubicin 60mg/m2 (or Epirubicin 100 mg/m2) + Standard of Care chemotherapy and drugs

Anthracycline Doxorubicin 60mg/m2 (or Epirubicin 100 mg/m2) + Standard of Care chemotherapy and drugs + Thermotherapy. Thermotherapy at first 3 chemotherapy treatments for Anthracycline chemotherapy nominally every 21±7 days plus Standard of Care chemotherapy. (A targeted tumor temperature of 44ºC (plus or minus 1.5ºC) and a targeted thermal dose of 80 equivalent treatment minutes (plus or minus 20 treatment minutes)). In the event that the targeted minimum cumulative thermal dose of 180 equivalent treatment minutes is not achieved in the first three treatments, an optional fourth thermotherapy treatment may be administered in combination with the fourth course of Anthracycline and standard of care chemotherapy. Standard of care (including breast imaging, drugs, and radiation) will be provided to all eligible subjects during and following the above study treatments.

Focused Microwave Thermotherapy

Anthracycline Doxorubicin 60mg/m2 (or Epirubicin 100 mg/m2) + Standard of Care chemotherapy and drugs. Anthracycline chemotherapy nominally every 21±7 days. Standard of care (including breast imaging, drugs, and radiation) will be provided to all eligible subjects during and following the above study treatments.

Chemotherapy (control)

Deborah Moorad-Watts

William C Dooley, MD

John R Keyserlingk, MD

William C. Dooley, MD

John Keyserlingk, MD

The purpose of this randomized Phase III study is to determine whether preoperative focused microwave heat treatment and chemotherapy combined are more effective than preoperative chemotherapy alone in the treatment of large breast cancer tumors in the intact breast. Combining heat with chemotherapy before surgery might shrink the tumor so that it can be removed in a breast conserving surgery (lumpectomy) instead of a mastectomy.

This randomized multicenter Phase III clinical trial is intended to provide histopathological and clinical information on an innovative, minimally-invasive approach (focused microwave thermotherapy) to the preoperative treatment of breast cancer, using a minimally invasive focused microwave phased array device, the Medifocus, Inc. APA 1000 Breast Thermotherapy Treatment System (heat treatment). Subjects with large primary operable breast cancer, in the intact breast, with clinical tumor size greater than or equal to 3.5 cm (including tumor classification T2 or T3), clinically node negative N0 or node positive (N1 or N2) with distant metastasis (M1) or without distant metastasis (M0) will be randomized (ratio 1:1) to receive (1) preoperative thermotherapy combined with preoperative anthracycline-based combination chemotherapy and standard of care versus (2) preoperative anthracycline-based combination chemotherapy and standard of care alone. The anthracycline-based regimen will be limited to those of the current National Comprehensive Cancer Network (NCCN) guidelines for dose/drug/schedule at the time of patient enrollment. In both arms of the study, standard of care including breast imaging, drugs, and radiation therapy will be provided to all eligible subjects during and following the preoperative regimen. At the clinical discretion of the treating physician, subjects that are estrogen-receptor positive may receive Tamoxifen therapy the day following the completion of chemotherapy. Radiation therapy to the breast tissues and lymph nodes will be given as part of the standard of care for eligible subjects. Treatment Arm I (new arm) regimen includes three preoperative thermotherapy treatments at intervals corresponding to the first three cycles of anthracycline-based combination chemotherapy plus standard of care. The addition of preoperative thermotherapy to preoperative anthracycline-based combination chemotherapy may improve the tumor response rate in terms of shrinkage (the primary endpoint) and may increase the option to perform breast conservation (a secondary endpoint) compared to that achieved with preoperative anthracycline-based combination chemotherapy and standard of care alone. Note: Since there is no consensus combination drug regimen for neoadjuvant treatment of large breast cancer tumors, each study site will use its own standard of care which will include other chemotherapy/drug agents commonly used in combination with an anthracycline (Doxorubicin (trade name Adriamycin) or Epirubicin (trade name Ellence)), which is the study base drug type.

The rationale for including patients that have distant metastasis (M1) at enrollment in this study is as follows. Traditionally, patients with stage IV (metastatic) breast cancer and an intact primary breast tumor have been treated with chemotherapy and radiation for palliation of symptoms, because this metastatic condition is considered to be an incurable disease. In some cases, surgery has been considered for stage IV patients with large, symptomatic breast lesions to control local wound complications and to improve quality of life. However, four recent retrospective peer-reviewed studies have suggested that removing the primary tumor may lead to an improvement in overall survival.

The investigator or designee will fully explain the nature of the study to the subject, along with the aims, methods, anticipated benefits, potential hazards and discomfort that participation might entail. After the nature of the study has been explained and all the subject's questions have been answered, and if the subject agrees to participate in the study, the informed consent will be reviewed and signed by the subject.

Each subject will be treated by thermochemotherapy (new arm) or chemotherapy alone (control arm) and followed for 90 days after surgery during the study. Patients will be followed annually as practiced as standard of care by each participating institution - patients will be followed for tumor recurrence and future medical intervention related to the patient's breast cancer.

Thermotherapy is administered in an out-patient setting. During thermotherapy which is completed in approximately 60 minutes or less, the patient is treated in the prone position on a treatment bed. After administering a local anesthetic, to guide the treatment a minimally invasive combination microwave/temperature probe is placed in the tumor under ultrasound guidance. The thermotherapy treatment is adjusted in accordance with patient comfort.

Anthracycline-based chemotherapy will be administered in accordance with standard preoperative chemotherapy delivery at each study center - the number of chemotherapy cycles and cycle timing may vary in this study. Each study center will be using anthracycline (Doxorubicin or Epidoxorubicin) as the base chemotherapy agent and the other chemotherapy agents and drugs will vary depending on the study center and subject specific needs. Each cycle of Doxorubicin at 60 mg/m2 for four cycles or Epidoxorubicin at 100 mg/m2 for 6 cycles and combination Standard of Care chemotherapy will be administered nominally every 21 (plus or minues 7) days. The timing between cycles of anthracycline can be subject specific at the physician's discretion, but in no case will anthracycline be administered with a cycle timing of less than seven (7) days between anthracycline cycles. A thermotherapy session will be administered on the same day as the administration of the first, second, and third cycle of preoperative Doxorubicin or Epidoxorubicin chemotherapy. Chemotherapy will be administered and then the subject will receive thermotherapy. (If the thermotherapy session cannot be administered on the same day as Doxorubicin or Epidoxorubicin chemotherapy it will be administered as soon as possible the following day but no later than 36 hours post Doxorubicin or Epidoxorubicin chemotherapy. The remaining cycle(s) of chemotherapy will then be administered without thermotherapy. If the desired cumulative minimum thermal dose is achieved in the first three thermotherapy treatments, the remaining cycle(s) of chemotherapy will then be administered without thermotherapy. If the desired cumulative minimum thermal dose is not achieved during the first three preoperative Doxorubicin or Epidoxorubicin chemotherapy cycles, thermotherapy will be administered with the fourth cycle of preoperative chemotherapy. If the subject cannot tolerate more than one or two thermotherapy treatments, the subject will continue in the study on the remaining cycles of chemotherapy. If the subject has clinically progressive disease, the thermo-chemotherapy treatment will be discontinued and the subject will receive the remaining cycles of chemotherapy preoperatively or postoperatively (as standard care).

At the end of the course of thermo-chemotherapy or chemotherapy alone, and following all pre-surgery evaluations, the surgeon and subject will make decisions on the extent of surgery to be performed. These decisions will be made on the basis of surgical and institutional standards, and those of the National Comprehensive Cancer Network (NCCN) Breast Cancer Treatment Guidelines. Subjects will undergo mastectomy or breast-conserving surgery. It is understood that some subjects will select mastectomy for treatment even when the surgeon recommends breast conservation. The surgeon shall document the reasons why either mastectomy or breast conservation was selected.

The subject will undergo clinical exam and imaging of the breast to measure tumor size, the day prior to or the day of the lumpectomy or mastectomy. Any additional imaging will be at the discretion of the physician. At the discretion of the physician, an optional core biopsy of the tumor will be taken the day prior or the day of the surgery.

Following surgery, pathology will be performed on the excised breast tumor tissue to determine tumor cell death. For breast conservation, the breast must be of sufficient size to allow adequate tumor removal with a satisfactory cosmetic result. The objective of surgery is to obtain local control of the breast cancer with the best cosmetic result possible. A breast conservation surgery procedure requires excision of the tumor and margins without removal of more normal breast tissue than is required to achieve negative margins. Pathologic evaluation of the excised tissue will determine whether the margins are negative or positive. For subjects with involved margins following breast conservation surgery, if the breast will tolerate it, the subject may undergo one or more further segmental resections in order to achieve clear margins.

Randomized Study of Combination Chemotherapy With or Without Focused Microwave Thermotherapy Before Surgery in Treating Women With Large Breast Cancer Tumors

Randomized Pivotal Trial to Assess the Safety and Efficacy of Preoperative Focused Microwave Thermotherapy Plus Preoperative Chemotherapy Versus Preoperative Chemotherapy Alone for Cytoreduction of Large Breast Cancer in Female Patients With Intact Breast

Evaluate the efficiency of preoperative focused microwave thermotherapy as an adjunct to chemotherapy to increase the ultrasound-measured absolute mean tumor percent shrinkage by volume over that achieved by SOC preoperative chemotherapy.

Evaluate the potential benefits of this combination treatment to increase the absolute rate for which the surgeon can recommend breast conservation (lumpectomy or partial mastectomy) over that achieved using standard of care preoperative chemotherapy alone.

Evaluate the potential benefits of this combination treatment to increase the clinical (caliper-measured) absolute mean tumor shrinkage by area over that achieved by SOC preoperative chemotherapy

Evaluate the potential benefits of the combination treatment to increase the absolute mean tumor shrinkage by area on mammography over the achieved by SOC preoperative chemotherapy

Evaluate the potential benefits of this combination treatment to increase the absolute mean tumor shrinkage by volume based on magnetic resonance imaging (MRI) over that achieved by SOC preoperative chemotherapy.

Evaluate the potential benefits of this combination treatment to increase the absolute mean percent localized pathologic tumor cell kill by volume over that achieved by SOC preoperative chemotherapy.

Medifocus, Inc.

Pathologic Complete Response

After radiologic complete remission at the end of NAST all patients will be treated with breast-conserving surgery alone without any axillary surgery. Approximately 80% of these patients will be assigned to the single study arm (no axillary SLNB) due to breast pCR (ypT0/ypTis) at the final pathology of lumpectomy.

After radiologic complete remission at the end of NAST all patients will be treated with breast-conserving surgery alone without any axillary surgery.

omission of SLNB

Toralf Reimer, Prof.

Oreste D Gentilini, MD

Florentia Peintinger, Prof.

Bernhard Heinrich, Dr.

Nina Ditsch, Prof. Dr.

Antje Hahn, MD

Anke Kleine-Tebbe, Dr.

Silke Polata, Dr.

Robert Radkowski, Dr.

Henning Eichler, Dr.

Hans-Christian Kolberg, PhD

Stefan P Renner, Prof.

Nikola Bangemann, Dr.

Stefan Ollig, MD

Stephan Hasmüller, MD

Oliver Hoffmann, PD

Alexander Hein, PhD

Christoph Lindner, Prof. Dr.

Ulrike Dörste

Thomas Müller, Prof. Dr.

Kundu Sudip, PhD

Elna Kuehnle, Dr.

Jörg Heil, Prof. Dr.

Sybille Perez, Dr.

Sabine Schmatloch, Dr.

Franziska Thiele, Dr.

Uta Fahl, Dr.

Agnieszka Nolte, Dr.

Angrit Stachs, PhD

Tamene Abraham, Dr.

Nicole Stahl, Dr.

Kilian IC Paukert, Dr.

Andrea Stefek, Dr.

Susanne Renz, Dr.

Michael Eichbaum, Prof.

Carolin Hammerle, Dr.

Hans-Joachim Strittmatter, Prof. Dr.

Antje Nixdorf, Dr.

Oreste D Gentilini, Dr

Isabel Rubio, Dr.

Currently, axillary surgery for breast cancer is considered as staging procedure that does not seem to influence breast cancer mortality, since the risk of developing metastasis depends mainly on the biological behaviour of the primary (seed-and-soil model). Based on this, the postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement.

Improvements in systemic treatments for breast cancer have increased the rates of pathologic complete response (pCR) in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR.

The investigators designed a clinical trial in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the planned trial, axillary surgery will be eliminated completely (no axillary sentinel lymph node biopsy \[SLNB\]) for initially cN0 patients with radiologic complete remission (rCR) and a breast pCR as determined in the lumpectomy specimen.

The trial design is a multicenter single-arm study with a limited number of patients (N=350) which might give practice-changing results in a short period of time, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over a period of 48 months.

EUBREAST-01 is a prospective non-randomized, single-arm surgical trial. Included patients will be recruited for the experimental arm (no axillary SLNB in cases with breast pCR after NAST) exclusively. EUBREAST-01 is an international multicentric trial and designed by European Breast Cancer Research Association of Surgical Trialists (EUBREAST). The University Medicine Rostock (Germany) will overtake the sponsorship for the trial.

Duration of recruitment is 4 years among 36 German, 10-15 Italian, 3 Spanish, and 1 Austrian study centres. The total number of patients to be recruited into the trial will be 350. All participating centres are experienced in conduction of clinical trials and stated at least a rate of 50 primary breast cancer diagnosis per year. At least 30% of all primary breast cancer are TNBC or HER2-positive tumors. The great majority of these cases will be diagnosed in tumor stage T1-T3. The NAST with chemotherapy (plus anti-HER2 therapy if HER2-positive) is standard for this cohort in Germany, Austria, Italy, and Spain.

Efficacy analyses will be conducted after a follow-up of at least 3 years for each patient regarding the primary and for the secondary outcomes. No interim analysis is planned. Patients will be assessed for disease recurrence according to standard national clinical practice. Longest follow-up is 7 years. History and physical examination will be performed every 6 months for the first 36 months and yearly thereafter. Annual mammography and sonography will be required; other testing will be based on symptoms and investigator preference.

Omission of SLNB in Triple-negative and HER2-positive Breast Cancer Patients With rCR and pCR in the Breast After NAST

Omission of Sentinel Lymph Node Biopsy in Triple-negative and HER2-positive Breast Cancer Patients With Radiologic and Pathologic Complete Response in the Breast After Neoadjuvant Systemic Therapy: a Single-arm, Prospective Surgical Trial.

no tumor in the ipsilateral breast or ipsilateral supraclavicular, infraclavicular, internal mammary or axillary nodes

European Breast Cancer Reseach Association of Surgical Trialists

University Medicine Rostock, Rostock, Germany (sponsor)

Else Kröner-Fresenius-Stiftung (funding)

German Society of Senology (funding)

Toralf Reimer, MD PhD

Deputy director, Department of Obstetrics and Gynecology

When there is no residual tumor cells on the vacuum-assisted biopsy specimen, breast surgery will be omitted. In the case of clinical N0 AND MRI size ≤ 0.5cm AND lesion-to-background signal enhancement ratio ≤1.6, sentinel lymph node biopsy will be omitted. Otherwise, sentinel lymph node biopsy will be performed. If necessary, axillary lymph node dissection will be performed.

For patients who are expected to achieve pathologic complete response after neoadjuvant chemotherapy based on MRI findings, vacuum-assisted biopsy will be performed on the main primary lesion marked with a clip. In case of pCR on vacuum-assisted biopsy specimen, breast surgery will be omitted.

Breast surgery omission

Han-Byoel Lee

Hong-Kyu Kim

A prospective, multicenter, single-arm non-inferiority trial to demonstrate that breast cancer patients who are predicted to have a pathologic complete response on MRI and vacuum-assisted biopsy after neoadjuvant systemic therapy, and are omitted breast surgery have a non-inferior 5-year disease-free survival compared to those who had received breast surgery.

\[Background \& Rationale for Study\]

Optimization (rather than de-escalation) of surgery for breast cancer is essential for our patients, and thus it is an important topic discussed actively in all major conferences regarding breast cancer and oncology.

A previous study showed that lesion-to-background parenchymal signal enhancement ratio (L-to-B SER) ≤1.6 and/or size ≤ 0.2cm on breast MRI can distinguish pathological complete response (pCR) from minimal residual cancer following neoadjuvant systemic therapy (NST). In a separate prospective study, 40 patients with near pCR (either tumor size ≤ 0.5 cm or L-to-B SER ≤ 1.6 on MRI) were enrolled and evaluated for the accuracy of US-guided biopsy aided by MRI in predicting pCR in the breast after NST. US-guided multiple core needle biopsy (CNB) or VAB of the tumor bed, followed by standard surgical excision, was performed. Matched biopsy and surgical specimens were compared to assess pCR. In result, obtaining at least 5 biopsy cores based on tumor size ≤ 0.5 cm and an L-to-B SER of ≤ 1.6 on MRI resulted in 100% NPV and accuracy. No differences in accuracy were noted between CNB and VAB (90% vs. 90%). It was demonstrated that patients who meet these stringent criteria on MRI may forego surgery for breast cancer.

Also, a pooled analysis of data from The Royal Marsden, MD Anderson Cancer Center, and Seoul National University Hospital showed that a VAB obtaining at least 6 cores for a lesion ≤2cm on imaging after NST can accurately predict pCR at a FNR of 3.2%.

For patients who would not benefit from surgery, it is unnecessary in terms of both personal and national medical expenses. Therefore, in order to establish the rationale for whether surgery could be omitted for patients with predicted pCR, it is necessary to demonstrate that the survival rate of patients who skipped breast surgery after confirming no residual cancer on VAB is non-inferior than that of patients who underwent breast surgery.

\[Study Objectives\]

To show non-inferiority in terms of disease-free survival (DFS) of omission of breast surgery for breast cancer patients who show no residual tumor on VAB after NST.

\[Study design\]

Prospective, multicenter, single-arm, non-inferiority trial

Omission of Breast Surgery for Breast Cancer Patients With pCR on MRI and Vacuum-assisted Biopsy After NST (OPTIMIST)

Omission of Breast Surgery for Predicted Pathologic Complete Response Patients With MRI and Vacuum-assisted bIopsy in Breast Cancer After Neoadjuvant Systemic Therapy: a Multicenter, Single-arm, Non-inferiority Trial

Available on Request (hblee80@gmail.com; hblee.md@snu.ac.kr)

Proportion of patients with no disease recurrence (including loco-regional recurrence, distant metastasis, and contralateral breast cancer) or death.

Proportion of patients with no disease recurrence in the ipsilateral breast or death

Proportion of patients with no invasive disease recurrence (including loco-regional recurrence, distant metastasis, and contralateral breast cancer) or death.

Analysis of QoL survey (BREAST-Q), procedure-related symptoms, and medical cost

Proportion of patients with metastatic lymph nodes among those with pCR on VAB

Ministry of Health & Welfare, Korea

Seoul National University Hospital

Omitting Axillary Lymph Node Dissection (ALND) in SrLNB-proven axillary complete response patients.

Finishing regional lymph node irradiation (RNI) including the axilla after surgery.

Before NST, positive lymph nodes would be marked with localized titanium clips under ultrasound guidance, and carbon nanoparticles suspension would be injected into the cortex of the marked lymph nodes and surrounding suspicious lymph nodes for staining. Marked and stained lymph nodes will be removed and biopsied after NST.

Stained region Lymph Node Biopsy (SrLNB)

RNI including the axilla covers the supraclavicular region and entire axillary lymphatic drainage area (region I, II and III) ,and is at a dose of 50 Gy/25 times, with additional prophylactic irradiation of the internal breast lymphatic drainage area for eligible patients.

Regional lymph node radiotherapy (RNI) including the axilla

Jue Wang, MD

Lingjun Ma, MD

Lingjun Ma

This prospective, single-arm, phase II trial studies axillary lymph node dissection (ALND) to see if it can be safely omitted in breast cancer patients with axillary pathological complete response (pCR) after neoadjuvant systemic therapy (NST). Breast cancer patients with biopsy-proven positive axillary lymph nodes at initial diagnosis, and converted to negative after NST, which is confirmed by Stained region Lymph Node Biopsy(SrLNB), will be enrolled in the study. In other words, a total of 92 patients will be exempted from ALND after SrLNB, and afterwards complete regional node irradiation (RNI) including the axilla. They will also undergo adjuvant chemotherapy, targeted therapy, endocrinotherapy after surgery. These patients will be followed up in the next three years for local-regional recurrence and long-time survival outcome.

Omission of ALND in Breast Cancer Patients With Axillary pCR

Omission of Axillary Lymph Node Dissection in Breast Cancer Patients With Axillary Pathological Complete Response After Neoadjuvant Systemic Therapy

Time interval from the surgery to invasive local-regional recurrence, distant metastasis, contralateral invasive breast cancer, or death from any cause.

This includes both local and regional recurrences. Local recurrence is defined as recurrence in the ipsilateral breast, chest wall, skin or surgical scar. Regional recurrence is defined as recurrence in the affected lymphatic drainage area, including the axilla, supraclavicular region, subclavicular region, and internal mammary node area.

Objective evaluation of upper limb lymphedema by arm circumference and bioelectrical impedance measurement. In our study, BCRL is diagnosed in two ways：① Relative Volume Change (RVC ) \>10% in the affected upper extremity. ②Bioelectrical impedance technology: the impedance ratio is defined as the ratio of the impedance of the healthy upper limb to the impedance of the affected upper limb, and BCRL is diagnosed when the patient's impedance ratio is higher than the mean + 2 standard deviations (SD) of healthy controls. When the two measurements are inconsistent, the former results shall prevail.

Patients' subjective assessment of quality of life (QoL) using the Functional Assessment of Cancer Therapy-Breast (FACT-B) . FACT-B is divided into 36 items in 5 domains, namely: physical status (7 items), social/family status (7 items), emotional status (6 items), functional status (7 items) and additional concerns, and each item is classified into five levels: not at all (0), somewhat (1), somewhat (2), fairly (3) and very much (4). Positive items were scored directly from 0 to 4, while negative items (i.e., the larger the number of response options, the worse the quality of life) were scored in reverse. The total score of FACT-B scale ranges from 0 to 144, a higher score means a better quality of life for the patient.

Patients' subjective assessment of lymphedema using the Quick Disability of the Arm, Shoulder, and Hand (Quick DASH) questionnaires，Quick DASH consists of 11 items, and is a self-rating scale of daily functioning including social functioning and physical activity and upper extremity symptoms. Each item is divided into 5 levels, and the patient's score is calculated as score = \[(patient score/number of response items) - 1\] × 25, with a total score of 0 to 100, and the higher the score, the greater the degree of upper limb dysfunction.

The First Affiliated Hospital with Nanjing Medical University

Prof.

Bone Density Conservation Agents

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Trastuzumab

Pertuzumab

Carboplatin

Capecitabine

Cyclophosphamide

Tamoxifen

Letrozole

Goserelin

Aromatase Inhibitors

Ranpirnase

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Antimetabolites

Antineoplastic Agents, Immunological

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

1. tamoxifen (+ LHRH analogue for premenopausal participant)
2. non-steroidal aromatase inhibitor (+ LHRH analogue for premenopausal participant)
3. Non-steroidal aromatase inhibitor in non-resectable tumor (+ LHRH analogue in premenopausal participant) + CDK4 / 6 inhibitor

1. 12 times weekly paclitaxel (80 mg / m˄2) followed by 4 times every 3 weeks epirubicin (E) (90-100 mg / m˄2) + cyclophosphamide (C) (600) (preferred)
2. 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then

   1. docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or
   2. 12x weekly paclitaxel (80mg / m˄2)
3. 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then

   1. 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or
   2. 12x weekly paclitaxel (80mg / m˄2)
4. TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)

1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then

   1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or
   2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab
2. Docetaxel (75 mg / m˄2) + carboplatin (AUC6) + trastuzumab +/- pertuzumab 6 times every 3 weeks c) E (90-100mg / m˄2) + C (600mg / m˄2) 4x every 2 weeks, then 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly)

1. Paclitaxel (80 mg / m˄2) +/- carboplatin (AUC2) 12 times weekly, then E (90-100 mg / m˄2) + C (600 mg / m˄2) 4 times three weekly (preferred)
2. 4x every 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then

   1. 4x docetaxel (90-100mg / m˄2) or
   2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2 )
3. 4x every 2 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then

   1. 4 times every 2 weeks paclitaxel (175 mg / m˄2) or
   2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2)

Letrozole 2.5Mg Tab

cyclophosphamide

paclitaxel

trastuzumab

pertuzumab

gabor Rubovszky

Balazs Madaras

Gabor Rubovszky, Ph D

Gabor Rubovszky

Observational investigation of participants who are given neoadjuvant treatment for invasive breast cancer. The scope of the study is to collect information on standardized treatment results, to explore the causes of dose modification and its effect on efficacy, to explore potential prognostic factors, and to explore the long-term side effects of different treatment modalities.

The purpose of the study is based on the uniform application of international guidelines in Hungarian conditions. The standardized circumstances may lead to optimization of neoadjuvant therapy, it may facilitate subsequent data analysis, provide a basis for prospective clinical questions, and demonstrate improvement in pathologic complete remission (pCR) and overall survival (OS) compared to historical control. It may make possible to collect real-life data on each therapeutic option: efficacy, side effects, dose reduction, dose intensity, long-term consequences. The main scope is to collect prospective data to explore prognostic and predictive factors. The auxiliary aim is the assessment and comparison of quality of life during specific treatments and their side effects.

Neoadjuvant Treatment of Breast Cancer

Neoadjuvant Treatment of Breast Cancer - a Prospective Observational Study, PANnon ONCology (PANONC) Group Non-commercial Clinical Trial

The individual participant data are not planned to be shared with other researchers but will be available upon request except personal data

study of the role of neutrophil/lymphocyte ratio (NLR) at baseline, before the 3. cycle, and before surgery. NLR is measured from the qualitative blood count as the absolute neutrophil count divided by the absolute lymphocyte count

monocyte/lymphocyte ratio (MLR) at baseline, before the 3. cycle, and before surgery. MLR is measured from the qualitative blood count as the absolute monocyte count divided by the absolute lymphocyte count

C-reactive protein serum level befor start of chemotherapy

circulating free-DNA at baseline, before 3. cycle, before surgery

from the beginning of neoadjuvant therapy to the first appearance of invasive tumor or death

Global health status, functional and symptom scales survey using the EORTC QLQ-C30 questionnaire before cycle 1, before cycle 4, after the last neoadjuvant chemotherapy, and before surgery, 1 year after chemotherapy

Breast cancer-specific functional scales and symptom scales survey using the EORTC QLQ BR45 questionnaire before cycle 1, before cycle 4, after the last neoadjuvant chemotherapy, and before surgery, 1 year after chemotherapy

to collect information all potential complaints and adverse event during and after treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Randomized Study of Combination Chemotherapy With or Without Focused Microwave Thermotherapy Before Surgery in Treating Women With Large Breast Cancer Tumors	NCT01204801	Breast Cancer	Focused Microwa... Chemotherapy (c...	18 Years -	Medifocus, Inc.
Omission of SLNB in Triple-negative and HER2-positive Breast Cancer Patients With rCR and pCR in the Breast After NAST	NCT04101851	Breast Cancer F... Breast Cancer	omission of SLN...	18 Years -	University of Rostock
Omission of Breast Surgery for Breast Cancer Patients With pCR on MRI and Vacuum-assisted Biopsy After NST (OPTIMIST)	NCT05505357	Breast Cancer I...	Breast surgery ...	20 Years -	Seoul National University Hospital
Omission of ALND in Breast Cancer Patients With Axillary pCR	NCT05939830	Axillary Lymph ... Pathological Co... Neoadjuvant Sys... Breast Cancer Axillary Lymph	Stained region ... Regional lymph ...	18 Years - 70 Years	The First Affiliated Hospital with Nanjing Medical University
Randomized Study of Combination Chemotherapy With or Without Focused Microwave Thermotherapy Before Surgery in Treating Women With Large Breast Cancer Tumors	NCT01204801	Breast Cancer	Focused Microwa... Chemotherapy (c...	18 Years -	Medifocus, Inc.
Neoadjuvant Treatment of Breast Cancer	NCT05131893	Breast Cancer	Tamoxifen Goserelin Letrozole 2.5Mg... Epirubicin cyclophosphamid... Docetaxel paclitaxel trastuzumab pertuzumab Capecitabine	18 Years - 100 Years	National Institute of Oncology, Hungary
Survival Benefit of Primary Tumour Resection Compared to Systemic Therapy Alone in Stage IV Colorectal Cancer Patients	NCT06326619	Colorectal Canc... Neoadjuvant Sys...	Primary tumor r... Systemic Therap...	-	Medizinische Hochschule Brandenburg Theodor Fontane
SURPASS Retrospective Study	NCT05779982	Breast Cancer Breast MRI Neoadjuvant Sys... Sentinel Lymph ...	Sentinel lymph ...	19 Years - 90 Years	Gangnam Severance Hospital

Spots Global Cancer Trial Database for neoadjuvant systemic therapy