Patient Question:Disease:Local recurrence after breast-conserving surgery? Description of disease:In July 2012, a painless mass of 1.9×1.7cm was found in the right breast, and a puncture biopsy was performed for invasive cancer. 2 negative, ki67-30%, postoperative 21 gene test was 50.09, 4 times of chemotherapy and 30 times of radiotherapy with EC protocol, (radiotherapy protocol: 3D-CRT technology, right breast residual breast tissue ten chest wall tissue for CTV, CTV head and foot and right-right external radiation 0.5cm (The radiation regimen: 3D-CRT technology, right breast residual breast tissue ten chest wall tissue for CTV, CTV head and foot and right-right external radiation 0.5cm, front and back external radiation 1.5cm for PTV, DT50Gy/25F/5W, post-tumor bed area electronic wire supplementation DT10Gy/5F/1W.), endocrine therapy was performed immediately after chemotherapy oral toremifene 60mg once a day until April 2015, routine review ultrasound in March 2015 found a 1.1×0.7cm mass below the incision margin of the right breast after breast conserving surgery, puncture for invasive cancer On April 26, 2015, the right breast was completely excised and reconstructed at the same time and the axillary lymph nodes were cleared. 2 1+, fiSh negative, Ki67-positive cells accounted for about 40%, P53-positive cells accounted for about 20%. I would like to help: Director Chen: Hello! My surgeon told me to have four cycles of adjuvant chemotherapy TC regimen: doxorubicinol 75mg/m2, cyclophosphamide 500-600mg/m2. now I have done 2 cycles of chemotherapy, adjuvant endocrine therapy: goserelin 10AI or TAM, do you think it is okay? The medical oncologist also said that I can use Goserelin 10 Al regimen for endocrine therapy without chemotherapy, but my surgeon insisted that I should have chemotherapy, and I couldn’t get in line for it. Which of the two endocrine treatment options is better to use? Do I need to remove my ovaries? Do I still need to do radiotherapy? I hope you will take time out of your busy schedule to help me! I am in pain, helpless and confused, please help me! Thank you! (A) Director Chen: Hello! My surgeon gave me four cycles of adjuvant chemotherapy TC regimen: doxorubicin 75mg/m2 and cyclophosphamide 500-600mg/m2. Now I have done 2 cycles of chemotherapy and adjuvant endocrine therapy: goserelin 10AI or TAM, do you think it is okay? The medical oncologist also said that I can use goserelin 10 Al regimen for endocrine therapy without chemotherapy, but my surgeon insisted that I should have chemotherapy, and I couldn’t get in line to consult you. A: I personally agree with your surgeon’s opinion. Chemotherapy + endocrine therapy. The reasons are: 1) Local recurrence of breast cancer after breast-conserving surgery, which is different from other site recurrence, has its own special characteristics because other site recurrence (e.g. distant metastasis) belongs to incurable disease, while local recurrence after breast-conserving surgery belongs to potentially curable patients (see 2012 European ESMO guidelines for the treatment of advanced breast cancer); because it belongs to potentially curable disease, its treatment strategy should be based on “adjuvant strategy” (i.e., pseudo-adjuvant strategy – see 2012 ESMO guidelines) rather than a salvage treatment strategy. And in your case, its adjuvant strategy would personally suggest chemotherapy + endocrine therapy. Why choose chemotherapy? It is because: (1) Patients with local recurrence have a higher risk of distant metastasis over the next 10 years than primary tumors with the same TNM stage, more than 36-44%. (See Int J Radiat Oncol Biol Phys 2001; 51:74-80; Eur J Cancer 2005; 41:2637-44.) (2) Your recurrent tumor Ki67 is more than 14-20% and is of luminalB1 type. (2) The CALOR trial subgroup analysis data is flawed: why do medical oncologists only use endocrine therapy? In fact, their opinion is not unfounded. It is based on the CALOR trial, which studied mainly whether you need to add chemotherapy in your case, and the result of its subgroup analysis showed that for ER+ patients, it is not significant to add chemotherapy. Therefore, this data was accepted by the 2014 International Breast Cancer ABC2 experts, who adopted the subgroup analysis data of the CALOR trial and did not believe that you needed chemotherapy for ER+ patients with endocrine therapy only. (See the “Local Recurrence” section of the 2014 ABC2 guidelines). (3) However, I personally do not agree with the ABC2 experts’ interpretation of the CALOR trial for the following reasons: 1) the sample size of the CALOR trial is too small, with only 162 patients enrolled; 2) ER+ is a subgroup analysis; and 3) the follow-up time of 4.9 years is still short for ER+ patients. Therefore, the conclusion that “ER+ does not benefit from chemotherapy” is not credible. My reasons for choosing chemotherapy have already been stated above. (b) Can I use tamoxifen (TAM) for endocrine therapy in my case? Which of the two endocrine therapy regimens is better to use? Do I need to have my ovaries removed? Do I still need to do radiotherapy? I hope you will take time out of your busy schedule to help me! I am in pain, helpless and confused, please help me! Thank you! A: 1) Can TAM continue to be used? A: No. The reason is that TAM and toremifene are both estrogen receptor modulators (SERMs), and there is cross-resistance between them. 2) Since TAM is not an option, AI is the preferred choice. However, if you choose AI, you are a premenopausal patient, so ovarian suppression (OFS) + AI is necessary. 3) What is the ovarian suppression method of choice? Currently, the main methods of ovarian suppression are pharmacological (classical drugs such as goserelin and leuprolide), surgical oophorectomy and radiotherapy as you mentioned. Radiation therapy has basically been eliminated from clinical practice because of its incomplete ovarian suppression and its tendency to cause intestinal adhesions. This leaves pharmacologic and surgical oophorectomy, which are equivalent in terms of efficacy (J Clin Oncol 1998; 16: 994C999.); the difference is that pharmacologic is non-invasive and has restorable ovarian function, whereas the latter is the opposite. You make a choice between these two approaches according to your personal wishes, and both are possible. 4) Assuming the choice of pharmacological (e.g. Norelide), when to give AI treatment? Personally, I recommend using Norelide for 4-6 weeks to observe whether estrogen levels reach menopausal status, and if so, add AI, if not, continue with Norelide alone until estrogen reaches menopausal status. The reason is: with pharmacologic ovarian function suppression, estrogen does not decrease immediately, but begins to decline after 3 weeks, or longer in some patients (J Clin Oncol 1989; 7: 1113C1119.); and AI is ineffective when used in a high estrogen state. 5) Which AI to choose? The third-generation AI currently in clinical use are letrozole, anastrozole and exemestane. The current evidence shows no difference in efficacy between the 3 (see MA27 trial), so they can all be chosen. However, I personally would prefer non-steroidal AI (e.g., letrozole, anastrozole) over exemestane. The reason is that there is no difference in the efficacy of such a choice, but in case of relapse later, there is a small difference in drug choice. The current second-line evidence is mostly focused on studies after first-line non-steroidal AI (such as BOLERO2, SOFEA, EFCET, etc.) to have the whole consideration. (iii) Regarding the choice of chemotherapy regimen Although you have used anthracycline in the past, the disease-free interval has been 3 years and anthracyclines are not off-limits. However, I personally fully agree with your surgeon’s design, which is the 4TC regimen (USON9735). The reasons are: although you have recurrent disease, the tumor is small, the lymph nodes are not metastatic, ER/PR expression is more than 50%, there is no need to design a chemotherapy regimen as strong as anthracycline + paclitaxel; 2) anthracycline was used in the past, although there is no evidence of its resistance to anthracycline, but the risk of potential resistance still exists. (iv) Is it radiotherapy? There is no prospective evidence to confirm the efficacy of re-radiotherapy in patients with previous radiotherapy, especially for such a small recurrent foci and complete surgical resection, and I personally do not actively recommend radiotherapy. Based on the above analysis, my personal treatment plan: sequential ovarian function suppression (OFS) + AI after 4TC chemotherapy, with the choice of OFS based on your weighing of the disadvantages of both, and the need to monitor estrogen levels if you choose pharmacological ovarian suppression. These comments are for your use only when discussing treatment options with your physician and for no other purpose!