Neoadjuvant Therapy+Surgery Together

Neoadjuvant Therapy Plus Surgery TogetherNeoadjuvant Therapy Plus Surgery Together

Preoperative systemic therapy may benefit certain high‑risk breast cancer patients1,2,a

Find out why.

Neoadjuvant therapy is systemic therapy given before surgery to
help downstage the tumor, optimize surgical outcomes, and may reduce the risk of breast cancer recurrence.3

Types of systemic
neoadjuvant therapy

Types of systemic
neoadjuvant therapy

  • CHEMOTHERAPY: A number of therapies are used as neoadjuvant therapy; regimens used in the adjuvant setting may be considered in the neoadjuvant setting.1
  • ENDOCRINE THERAPY: May be offered to those with strongly hormone-receptor–positive tumors.1
  • HER2-TARGETED THERAPY: Chemotherapy plus targeted HER2 agents may be used for neoadjuvant therapy in HER2+ breast cancer treatment.1

HER2 = human epidermal growth factor receptor 2.

What is high-risk
breast cancer?

What is high-risk breast
cancer?

Learn why this surgical oncologist considers neoadjuvant therapy
Monica Morrow, MD
Surgical Oncologist
Potential preoperative benefits include:
  • Downstaging the tumor2,3
  • Decreasing the degree of nodal involvement4,5
  • Minimizing the extent of axillary surgery and subsequent postoperative complications, such as lymphedema4,5
  • Allowing time for genetic testing3
  • Conserving breast tissue2,3
  • Improving breast cosmesis4
  • Assessment of tumor response to systemic therapy2,3
Potential long-term benefits in neoadjuvant patients who achieved a pathological complete response (pCR) (vs those who did not) include3,b:
  • Favorable event-free survival3
  • Favorable overall survival3,b

Patients with more aggressive subtypes have been shown to have an increased likelihood of achieving a pCR.2

Common Pathological Complete Response DefinitionsCommon Pathological Complete Response Definitions
Two common definitions of pCR2:
  • Absence of invasive cancer and in situ cancer in the breast and axillary nodes
  • Absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ
Find out whether neoadjuvant therapy is used in all appropriate patients
Heather McArthur, MD
Medical Oncologist
 

Consider Neoadjuvant Therapy

for high-risk patients, such as stage II
and stage III TNBC and HER2+ breast
cancer patients1,3,a

TNBC = triple-negative breast cancer;
HER2 = human epidermal growth factor receptor 2.
Consider Neoadjuvant Therapy for High-risk Patients, Such as Stage II and Stage III TNBC and HER2+ Breast Cancer PatientsConsider Neoadjuvant Therapy for High-risk Patients, Such as Stage II and Stage III TNBC and HER2+ Breast Cancer Patients

Find out more about which patients may be eligible.

Who May Be Appropriate
Neoadjuvant Patients?

Many stage II and III
patients with high-risk
breast cancer may be eligible
for neoadjuvant therapy3





See how this oncologist chooses appropriate patients
Heather McArthur, MD
Medical Oncologist
Who Are Potential Candidates for Neoadjuvant Therapy?
POTENTIAL CANDIDATES
FOR NEOADJUVANT
THERAPY
  • Patients with locally advanced or inoperable breast
    tumors3
    • Inflammatory breast cancer or
    • N2 and N3 regional lymph node nodal disease or
    • T4 tumor
  • Patients with operable breast cancer who are clear candidates for adjuvant chemotherapy3
    • Patient desires breast-conserving surgery but not possible due to the size of the tumor relative to that of the breast, with the hope that this will help obtain clear surgical margins at final resection or3
    • Patients with node-positive disease likely to become node negative with preoperative systemic therapy3
    • Breast cancer subtype is associated with an increased likelihood of response (eg, TNBC, HER2+)2

N = node; T = primary tumor; TNBC = triple-negative breast cancer;
HER2 = human epidermal growth factor receptor 2.

N = node; T = primary tumor; TNBC = triple-negative breast cancer; HER2 = human epidermal growth factor receptor 2.

INAPPROPRIATE PATIENTS FOR
NEOADJUVANT THERAPY3
  • Extensive in situ disease when the extent of invasive disease cannot be defined.
  • Extent of the tumor is poorly delineated.
  • Tumors are not palpable or clinically assessable.
Neoadjuvant systemic therapy may be considered for any patients for whom adjuvant systemic therapy is indicated, and the decision to use it should be made in collaboration with a multidisciplinary team.3,6
Discover how this surgeon works with her multidisciplinary team
Monica Morrow, MD
Surgical Oncologist

Clinical Data
in
Neoadjuvant
Treatment

Potential benefits of
neoadjuvant therapy for
patients and health care
professionals2–4,7

PREOPERATIVELY

REAL-TIME evaluation of patient response to systemic therapy to help guide future therapeutic decisions2,3

ACHIEVE tumor or nodal downstaging to increase tumor resectability and decrease surgical morbidity4

INCREASE the feasibility of breast-conserving surgery (BCS) among mastectomy candidates with stage II and III disease4

INCREASE feasibility of sentinel node biopsy in formerly node-positive disease4

DECREASE the morbidity and extent of axillary surgery in bulky node-positive disease4

IMPROVE cosmesis among BCS candidates4

ACHIEVE pathological complete response (pCR)2,3,b

POSTOPERATIVELY

FAVORABLE event-free survival in patients who achieve pCR (vs those who have not)3

FAVORABLE overall survival in patients who achieve pCR (vs those who have not)3

Considerations and Potential Concerns Associated With Neoadjuvant Treatment
  • Consider the potential concerns associated with neoadjuvant treatment for early breast cancer3,8
    • Risk of disease progression during preoperative systemic therapy
  • Reduced window of opportunity for fertility preservation8
  • Accurate clinical staging at baseline is essential before initiating neoadjuvant treatment3,8
    • There is a risk of overtreatment with systemic therapy if patient’s clinical stage is overestimated
    • There is a risk of undertreatment with certain therapies if patient’s clinical stage is underestimated
 

Patients with the subtypes of TNBC and HER2+ breast cancer may be more likely to achieve pCR with neoadjuvant therapy vs patients with other subtypes.2

An analysis of 12 international trials of neoadjuvant treatment of patients with breast cancer (N=11,955), designed to determine if pathological complete response (pCR) could be used as a surrogate end point for event-free survival or overall survival. Three of the most commonly used definitions of pCR were utilized for the analysis.2,c

cDefinitions of pCR included: 1. absence of invasive cancer and in situ cancer in the breast and axillary nodes; 2. absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ; and 3. absence of invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement.2

Tumor subtypes and percentage of patients achieving pCR, (95% CI)2

  • HER2+/HR+ (n=1,086)d

    18.3 (15.5–21.3)
    – to –
    30.9 (26.3–35.8)

  • HER2+/HR- (n=835)d

    30.2 (26.0–34.5)
    – to –
    50.3 (45.0–55.5)

  • TNBC (n=1,157)

    33.6 (30.9–36.4)

  • HR+/HER2- (n=2,616)e

    7.5 (6.3–8.7)
    – to –
    16.2 (13.4–19.3)

  • dpCR rates differ based on treatment regimens utilized.
  • epCR rates differ based on grade of disease.
 




Consider Neoadjuvant Therapy

for high-risk patients, such as stage II
and stage III TNBC and HER2+ breast
cancer patients1,3,a

Consider Neoadjuvant Therapy for High-risk Patients, Such as Stage II and Stage III TNBC and HER2+ Breast Cancer PatientsConsider Neoadjuvant Therapy for High-risk Patients, Such as Stage II and Stage III TNBC and HER2+ Breast Cancer Patients

  • a“High-risk” defined as early-stage breast cancer patients who have a high risk of distant disease recurrence and death despite use of optimal modern local and systemic adjuvant therapy.7
  • bCTNeoBC pooled analysis: 12 international trials of 11,955 patients with breast cancer treated with preoperative chemotherapy followed by surgery, with available data for EFS, OS, and pCR; pCR was not the primary end point for evaluation. Three most commonly used definitions of pCR were evaluated for their association with EFS or OS. Patients who attained pCR demonstrated improved EFS and OS vs those who had residual disease. The prognostic value was greatest in aggressive tumor subtypes, particularly TNBC and HER2+ breast cancer.2

CTNeoBC = Collaborative Trials in Neoadjuvant Breast Cancer; EFS = event-free survival; HER2 = human epidermal growth factor receptor 2; HR = hormone receptor;
OS = overall survival; TNBC = triple-negative breast cancer.

  • References:
  • 1. Wirapati P, Sotiriou C, Kunkel S, et al. Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res. 2008;10(4):R65. doi:10.1186/bcr2124.
  • 2. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–172.
  • 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed September 24, 2018. To view the most recent and complete version of the guidelines, go online to NCCN.org.
  • 4. Holmes D, Colfry A, Czerniecki B, et al. Performance and practice guideline for the use of neoadjuvant systemic therapy in the management of breast cancer. Ann Surg Oncol. 2015;22(10):3184–3190.
  • 5. Herd-Smith A, Russo A, Muraca MG, et al. Prognostic factors for lymphedema after primary treatment of breast carcinoma. Cancer. 2001;92(7):1783–1787.
  • 6. The American Society of Breast Surgeons. Performance and practice guidelines for the use of neoadjuvant systemic therapy in the management of breast cancer. https://www.breastsurgeons.org/statements/guidelines/PerformancePracticeGuidelines_NST.pdf. Published March 2, 2017. Accessed October 2, 2018.
  • 7. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for industry. Pathological complete response in neoadjuvant treatment of high-risk early-stage breast cancer: use as an endpoint to support accelerated approval. www.fda.gov/downloads/drugs/guidances/ucm305501.pdf. Published October 2014. Accessed September 27, 2018.
  • 8. Cain H, Macpherson IR, Beresford M, Pinder SE, Pong J, Dixon JM. Neoadjuvant therapy in early breast cancer: treatment considerations and common debates in practice. Clin Oncol. 2017;29:642–652.