[Interpretation 1] Adjuvant targeted drug therapy, refining the indications for trastuzumab application
The 2009 edition of the cNCCN guidelines continues to emphasize the important role of HER2 status in the selection of adjuvant therapy. For HER2-positive patients, a combination regimen containing trastuzumab should be considered for postoperative adjuvant therapy. For patients with tumor diameter ≥1 cm or positive lymph nodes, adjuvant trastuzumab therapy is recommended for 1 year.
However, compared with the 2008 edition of the guidelines, the 2009 edition has added the following.
(1) Consider systemic adjuvant therapy ± trastuzumab for patients with a primary tumor size of 0.6-1.0 cm and moderate to low differentiation or with poor prognostic factors. However, it is important to note that this is category 3 evidence.
(2) Patients with tumor stage T1a and T1b and negative lymph nodes usually have a better prognosis even if HER2 is amplified or overexpressed. This is a group of breast cancer patients who have not yet been studied in a randomized trial. Whether this group of patients is treated with trastuzumab must be considered in the context of the known toxicities of trastuzumab (e.g., cardiotoxicity), as well as the expected benefit from treatment that has not yet been determined.
(3) If HER2 positive, trastuzumab therapy should be completed for up to 1 year (Class 1 evidence). If indicated, trastuzumab may be used in parallel with radiotherapy or endocrine therapy. If capecitabine is used as a radiosensitizer, trastuzumab may be administered concurrently.
If neoadjuvant chemotherapy is required, trastuzumab-containing neoadjuvant chemotherapy should be considered for at least 9 weeks for patients with HER2 overexpression.
Interpretation 2]
The 2009 edition of the guidelines classifies adjuvant chemotherapy regimens into preferred and other. Additional regimens have been added, such as AC (doxorubicin combined with cyclophosphamide) sequential docetaxel regimens.
The new guidelines also add a number of footnotes.
(1) Patients with positive lymph nodes are preferred to anthracycline- and paclitaxel-containing chemotherapy regimens. Current clinical studies do not yet support the use of paclitaxel-containing regimens for lymph node-negative patients.
(2) The selection, dosage and application of anticancer drugs and the management of associated toxicity are complex. The presence of toxic reactions, individual differences, prior therapy and comorbidities necessitates changes in dose and regimen as well as the initiation of supportive therapy. Giving patients the best anti-cancer drug therapy requires a medical team with extensive experience in the application of anti-cancer drugs and the management of associated toxicities.
Interpretation 3] Endocrine therapy
Repeat testing at appropriate times to clarify receptor status
For breast cancer with good histological type, if estrogen receptor (ER) and progesterone receptor (PR) are negative, repeat testing is recommended to clarify the receptor status before deciding on the next step of adjuvant therapy. Similarly, repeat testing for receptor status may be indicated for ER and PR negative tumors with clinical features predicting possible hormone receptor positivity (e.g., long disease free interval, limited site of recurrence, slow disease progression, or older patient age).
Experimental endocrine therapy or chemotherapy may be considered for patients who are ER and PR negative and have only bone or soft tissue metastases or asymptomatic visceral metastases, if they are not resistant to endocrine therapy.
No emphasis on a particular choice of AI in a particular treatment strategy
Both the NCCN panel and Chinese experts agreed that.
(1) the antitumor effects and toxic responses of the three aromatase inhibitors (AI) anastrozole, letrozole, and exemestane are essentially similar, and the AI whose design is closest to the current clinical situation is the most appropriate choice for participation in clinical trials. The optimal duration of treatment is unknown.
(2) Some patients become amenorrheic during TAM treatment, but it is possible to restore ovarian function after discontinuation of TAM and initiation of AI therapy.
Therefore, plasma estradiol and follicle stimulating hormone (FSH) levels can be tested periodically in clinical practice. If ovarian function is restored, AI should be discontinued and TAM therapy switched, or AI should be continued after measures to suppress ovarian function. in accordance with these points, the 2009 edition of the guideline does not emphasize the particular choice of a particular AI in a certain treatment strategy.
【Interpretation 4】 Treatment of recurrent metastatic breast cancer
Adjustment of some drugs and regimens
The 2009 edition of the guideline makes adjustments to some drugs and regimens, including.
(1) Addition of cyclophosphamide and methotrexate to the other available options;
(2) Ixabepilone (evidence 2A) + capecitabine (evidence 2B) was included as a formal available option in other combination regimens;
(3) For HER2-positive metastatic breast cancer, prioritize drugs and regimens in combination with trastuzumab: in addition to paclitaxel ± carboplatin, docetaxel, and vincristine, capecitabine was newly added;
(4) For HER2-positive breast cancer with previous trastuzumab, the drug regimens prioritized are: lapatinib + capecitabine, trastuzumab + other first-line drugs, trastuzumab + capecitabine, and trastuzumab + lapatinib (without cytotoxic drug therapy).
Emphasize the principles of chemotherapy regimen selection
(1) Patients treated with adjuvant therapy only with endocrine therapy without chemotherapy can choose CMF (CTX/MTX/5-FU) or CAF (CTX/ADM)/AC (ADM/CTX) regimens, although this is rarely seen in clinical practice;
(2) The AT regimen (anthracycline combined with paclitaxel) is preferred for patients who have not used anthracycline and paclitaxel chemotherapy for adjuvant therapy, such as patients who have failed adjuvant therapy with the CMF regimen; some patients who have used anthracycline and/or paclitaxel chemotherapy for adjuvant therapy but have not been clinically determined to be resistant and have failed treatment may also use the AT regimen;
(3) Patients who have failed adjuvant anthracycline therapy can choose the following regimens: XT (capecitabine combined with docetaxel) and GT (gemcitabine combined with paclitaxel) regimens; patients who have failed paclitaxel therapy, there is no standard regimen recommended, and the drugs that can be considered are capecitabine, vincristine, ixabepilone, gemcitabine and platinum, taking single-agent or combination chemotherapy.
Recommended principles of endocrine drug selection
Principles of selection.
(1) Generally do not repeat the drugs used in adjuvant therapy or first-line therapy;
(2) AI is preferred in patients who have failed adjuvant tamoxifen therapy;
(3) Progestin (megestrol acetate/medroxyprogesterone) or fulvestrant may be chosen if AI treatment fails;
(4) TAM or toremifene may still be used in patients who have not been previously treated with anti-estrogen therapy;
(5) Premenopausal patients who are ER positive may be treated with ovarian function suppression and subsequently follow the guidelines for endocrine therapy in postmenopausal patients.
Baseline levels of bone mineral density should be measured regularly with bisphosphonates
Advanced breast cancer, if bone metastases are present, is usually treated with the addition of bisphosphonates. The new version of the guidelines recommends measuring baseline levels of bone mineral density prior to the use of bisphosphonates and repeating them periodically. The use of estrogen, progestin, or selective estrogen receptor modulators is not recommended for the treatment of osteoporosis or bone loss in women with breast cancer. The use of bisphosphonates is generally considered to be a more desirable approach to increasing bone mineral density. Current clinical trials support the use of bisphosphonates for up to 2 years. Extending their duration of treatment may increase the benefit, but has not been confirmed by clinical trials. Women treated with bisphosphonates should have a dental examination and preventive dental treatment before starting treatment, and should take calcium (1200-1500 mg/d) and vitamin D (400-800 IU/d) supplements.
[Interpretation 5] Other updates
RT-PCR routine testing is not recommended
The Chinese panel concluded that RT-PCR testing for 21 genes is only available as an optional test and is not recommended due to insufficient evidence and high cost.
Recommended postoperative mammograms not recommended for routine PET/CT scans
The new guidelines add a recommendation for genetic counseling for patients at high risk for hereditary breast cancer in the screening section. In addition, it is specifically stated that all patients should receive a post-excisional mammogram if there is doubt about the adequacy of the excision.
The panel does not recommend the routine use of PET or PET/CT scans in the evaluation of locally advanced disease unless the results of other staging methods are ambiguous or questionable. PET/CT scanning is not indicated for staging clinical stage I, II, or resectable stage III breast cancer.
[Conclusion
Based on the 2008 edition, the 2009 edition of cNCCN guidelines has updated the diagnosis and treatment of breast cancer, especially in the areas of targeted therapy, endocrine therapy, and the application of bisphosphonates, etc. These adjustments and instructions will undoubtedly be of great benefit to Chinese physicians in better clinical diagnosis and treatment.
As basic and clinical research on breast cancer progresses, a large number of randomized phase III clinical trials will be published every year, and these new evidence-based medical evidence will be reflected in various guidelines, including the cNCCN guidelines and St. Gallen consensus, thus will continue to refine, improve and even change the existing clinical practice.