Introduction and impact of the young breast cancer in China consensus

YBCC epidemiology

Studies indicate that breast cancer among young patients in China imposes an enormous disease burden for society. First, China has the largest global share of breast cancer in all age groups (15.6%) as well as young patients (13.2%)². Second, the proportion of young breast cancer patients in China is markedly higher than Western countries. Several large population studies showed that 15%–19.9% of breast cancer patients are < 40 years of age^4,5 and approximately 10% of patients are ≤ 35 years of age⁶. Moreover, the incidence of breast cancer in young patients increases by approximately 2% annually⁷. In fact, the median age of breast cancer onset in the United States is 62–64 years but the median age of breast cancer onset is much younger (45–49 years) in East Asia countries, including China^4,8.

Unmet needs of young patients with breast cancer in China

Definition of YBCC

Although the median age of breast cancer onset in China is 45–49 years, 62% of the YBCC panelists were of the opinion that the definition of young breast cancer is < 40 years, which is the same as the BCY international consensus, and 32% of the panelists chose < 35 years of age as the definition of young breast cancer. Consequently, a consensus was reached by YBCC expert panel to define young patients with breast cancer as < 40 years of age.

BRCA1/2 gene mutation

The YBCC experts were more conservative with respect to the indications for BRCA1/2 mutation testing. Of the panelists, 63% supported testing in young patients (< 40 years of age), 97% endorsed testing for patients with a family history of breast cancer, and 91% recommended testing for triple-negative breast cancer (TNBC). These outcomes reflect the different epidemiologic characteristics and socioeconomic status of the Chinese breast cancer population.

For young breast cancer patients with a BRCA1/2 mutation who are candidates for BCS, 72% of YBCC experts recommend that the surgical decision should be based on an individualized recurrence risk assessment, including age, family history, and personal preference. For patients with a BRCA1/2 mutation who will undergo a nipple-sparing mastectomy (NSM) with implant reconstruction, 66% of experts suggest the choice of contralateral prophylactic mastectomy should be made considering patient age, family history, and contralateral breast cancer risk. In addition, for patients with a BRCA1/2 mutation choosing BCS or not opting for contralateral prophylactic mastectomy, 82%, 71%, and 87% of experts recommend close surveillance with ultrasonography, mammography, and MRI, respectively.

The clinical utility of platinum-based chemotherapy in the adjuvant setting for BRCA1/2 mutation carriers is controversial but no consensus has been reached by the YBCC expert panel.

The decision regarding prophylactic bilateral salpingo-oophorectomy and the timing should consider the mutation type, family history, and personal preferences according to 72% of experts.

Chemotherapy

YBCC experts suggest that young patients, like the older patients, should have the chemotherapy regimen chosen based on factors, such as disease stage and molecular subtype, but not age. Choosing more aggressive chemotherapy solely due to younger age may pose a risk of overtreatment.

Of the YBCC panelists, 84% were in favor of the anthracycline-taxane sequential regimen for medium-high risk (defined as stage II or III with positive lymph nodes) human epidermal growth factor receptor 2 (HER2)-positive young breast cancer patients, while 70% of the panelists chose a taxane combined with platinum regimen in addition to dual HER2 blockade. Most panelists chose an anthracycline-taxane sequential regimen and only 17% of the panelists chose an anthracycline-free regimen consisting of six cycles of docetaxel and cyclophosphamide (6TC) for medium-high risk HER2-negative young breast cancer patients. Of the YBCC panelists, 71% were opposed to routinely considering platinum as a substitute for anthracyclines in adjuvant chemotherapy regimens for medium-high risk HER2-positive or TNBC young breast cancer patients.

Endocrine therapy

Hormone receptor (HR)-positive young breast cancer patients often need OFS to lower relapse risk. A gonadotropin-releasing hormone agonist (GnRHa) is the most frequently used drug to achieve OFS. Of the YBCC panelists, 81% supports both formulations as options for OFS when used together with selective estrogen receptor modulators (SERMs). However, 50% of the panelists were cautious when aromatase inhibitors (AIs) were used with a three month (3M) GnRHa in young patients because younger patients are more likely to experience OFS escape (defined as failure to achieve complete OFS with a GnRHa) due to potent ovarian function.

The optimal timing for initiating AI has not been established for patients using a GnRHa in combination with an AI. The YBCC expert panel has not reached a consensus on this issue with 43% recommending that AI should only be used after confirming ovarian suppression to avoid the increase in plasma estradiol levels caused by AI monotherapy when OFS is not successful. Nevertheless, 53% of YBCC panelists proposed simultaneous initiation of a GnRHa and AI when GnRHa begins to control hormone levels from the hypothalamic-pituitary axis because the stimulatory effect of an AI on the hypothalamic-pituitary pathway is limited.

Regular estradiol (E2) monitoring facilitates early detection and management of ovarian function escape, ensuring effective treatment. However, a unified frequency and standard for E2 monitoring have not been established in clinical practice. The YBCC expert panel did not reach a consensus because 45% did not support the routine monitoring of E2 levels in patients receiving GnRHa treatment.

Fertility preservation

The YBCC expert panel suggested that suitable fertility preservation strategies should be considered prior to initiating systemic therapy for young patients with desired fertility. In addition, a chemotherapy regimen without cyclophosphamide should be considered to minimize ovarian damage. A GnRHa, although not sufficient alone, should be used for ovarian protection during chemotherapy in addition to the aforementioned measures.

Gynecologic conditions

Of the YBCC panelists, 90% agreed that tamoxifen increases the risk of endometrial cancer in peri- and post-menopausal patients. However, 48% of the YBCC panelists never encountered a patient with endometrial cancer after tamoxifen use, indicating the low incidence of tamoxifen-related endometrial cancer in China. Moreover, 67% and 91% of the YBCC panelists supported regular monitoring of endometrial thickness in premenopausal and peri-/post-menopausal patients, respectively. However, the YBCC expert panel did not reach a consensus within the gynecologic community on the appropriate threshold for diagnostic curettage in asymptomatic patients receiving tamoxifen.

The YBCC expert panel did not reach a consensus on whether breast cancer patients can use progestin-containing intrauterine devices or long-term oral contraceptives due to the low level of existing evidence.

Guideline differences for young breast cancer patients

The YBCC consensus is more focused on the questions and needs in young Chinese patients compared to the comprehensive coverage of the BCY5 consensus²⁰. More importantly, the YBCC consensus references research data from the Chinese population and aligned recommendations with the Chinese context. The guidelines related to young breast cancer patients are summarized in Table 1, offering a comparative view of similarities and differences.