Breast Cancer (BC)

Treatment regimens

Primary operable (resectable) breast cancer (0, I, IIA, IIB, IIIA (T3N1M0) stages)

Recommended tactics for the treatment of primary operable breast cancer

Recommended Neoadjuvant therapy treatment sequence

Surgery

• It is preferable to perform organ-preserving surgery (sectoral resection, lumpectomy).
• If tumor elements are found in the resection margins, a second operation is recommended: an additional resection or mastectomy to achieve «cleanliness» of the resection margins in order to ensure local control of the disease.
• «Clean» is defined as the absence of non-invasive cancer at the distance of >2 mm from the resection margin.
• If necessary, performing a symmetrizing operation on the contralateral mammary gland for aesthetic purposes.
• If it is impossible to perform an organ-preserving operation, a mastectomy with primary breast reconstruction is performed.

Stage 0 (TisN0M0), ductal carcinoma in situ

If an invasive component is suspected in a breast tumor, it is advisable to perform a SLNL (sentinel lymph node biopsy).

Stages I (T1N0M0) and IIA (T2N0M0))

Surgery combined with SLNB

Stages IIA (T1N1M0), IIB (T2N1M0, T3N0M0), IIIA (T3N1M0)

Resection of the mammary gland with axillary lymphadenectomy. At stage T3N0, SLNB is performed to clarify the extent of breast cancer spread.

Radiation therapy

• Adjuvant RT is recommended after organ-preserving surgery.
• When HT and / or anti-HER2 therapy is prescribed, it is carried out simultaneously with RT.

Stage 0 (TisN0M0), ductal carcinoma in situ

It is not recommended to perform RT after mastectomy.

Stages I (T1N0M0) and IIA (T2N0M0)

RT after mastectomy in case of presence of tumor cells along the resection margin or at a distance less than 1 mm from the resection margin.

When HT and / or anti-HER2 therapy is prescribed, it should be carried out simultaneously with RT.

Stages IIA (T1N1M0), IIB (T2N1M0, T3N0M0), IIIA (T3N1M0)

RT after organ-preserving operations.

RT after mastectomy.

Drug therapy

• In case of positive ER and PR, tamoxifen is recommended to prevent the development of second tumors in the contralateral or resected (in case of organ-preserving surgery) mammary gland
• For postmenopausal patients with positive ER and PR, it`s required to consider HT with aromatase inhibitors
• In adjuvant therapy for in situ cancer (ductal or lobular), chemotherapy and ovarian suppression are not indicated

Adjuvant hormone therapy for breast cancer

Adjuvant HT is indicated for all patients with hormone-dependent breast cancer, regardless of age, ovarian function, disease stage, HER2 status, neo-/adjuvant chemotherapy or anti-HER2 therapy. Tumors with detectable ER expression in ≥ 1% of invasive breast cancer cells are considered hormone-dependent.

Locally advanced primary inoperable invasive breast cancer (stages IIIA (except T3N1M0), IIIB and IIIC)

Recommended tactics for the treatment of locally advanced primary inoperable breast cancer:

Neoadjuvant HT may be recommended for menopausal patients with luminal A subtype of breast cancer.

Adjuvant chemotherapy is not recommended for patients who have received neoadjuvant chemotherapy in full.

Breast cancer patients with a triple negative phenotype (negative ER, PR and HER2), who have received standard neoadjuvant chemotherapy with anthracyclines and taxanes in full, in case of an invasive residual tumor, are recommended to use capecitabin as postneoadjuvant CT.

Patients with HER2-positive breast cancer who have received standard neoadjuvant drug therapy with anthracyclines and / or taxanes in combination with trastuzumab (± pertuzumab), in case of an invasive residual tumor, are recommended to use trastuzumab emtansine as post-neoadjuvant therapy.

Pathological examination should include an assessment of the pathological response severity using the classification.

Metastatic breast cancer

Treatment is aimed at improving the quality of life and increasing its duration.

There is no single standard for the treatment of metastatic breast cancer.

The choice of drug therapy is carried out taking into account biological markers (expression of ER and PR, HER2, Ki67, PIK3CA mutations, PD-L1 expression, BRCA1/2 germline mutations) and clinical and anamnestic features of the patient.

Systemic therapy, if necessary, can be supplemented with local treatments (radiation and/or surgery).

Metastatic hormone-dependent breast cancer

Selection method — GT

Single line HT is performed until disease progression or signs of unacceptable toxicity.

The ineffectiveness of three consecutive lines of HT indicates resistance to this type of treatment and the need for chemotherapy.

Simultaneous use of CT and HT is not recommended.

CDK4/6 inhibitors: palbociclib / ribociclib/ abemaciclib

Metastatic HER2- BC

CT is indicated for the following categories of patients:

• breast cancer with negative ER and PR;
• luminal BC resistant to HT;
• luminal BC with signs of a visceral crisis.

BRCA1/2-associated HER2-negative metastatic breast cancer

After CT with anthracyclines and taxanes, PARP inhibitors (olaparib, talazoparib) are recommended.

HT in combination with CDK4/6 inhibitors is recommended to be used first.

Metastatic HER2+ breast cancer

Anti-HER2 therapy + CT or HT (for luminal tumors) or mono mode.

With the first episode of progression against the background of trastuzumab therapy, it is possible to continue treatment with the same drug with a change in the chemo-/ HT component

• Trastuzumab + pertuzumab + taxanes (preferred first-line regimen)
• Trastuzumab-emtansine
• Trastuzumab ± pertuzumab + paclitaxel / docetaxel/ vinorelbine / capecitabine / gemcitabine / cyclophosphamide / ixabepilone / eribulin / etoposide
• Trastuzumab mono
• Lapatinib

HER2-positive luminal breast cancer

• aromatase inhibitors + trastuzumab
• aromatase inhibitors + lapatinib
• aromatase inhibitors + trastuzumab + lapatinib
• fulvestrant + trastuzumab
• tamoxifen + trastuzumab