Breast cancer is rare in young women. Less than 0.1% of thousands of diagnosed breast cancer patients around the world are under the age of 20. 1.9% are between the ages of 20-34 and 10.6% are between the ages of 35-44 (1,2). Although the number of patients diagnosed with breast CA under the age of 40 is less than 7%, more than 14,000 patients annually are diagnosed with invasive or noninvasive breast cancer in the USA alone. Despite the increasing rates of mammography and lifestyle changes, the incidence of breast cancer has remained stable in the western world in the last decade (3-5). In addition, there is an increase in the incidence of breast cancer in young women in underdeveloped countries due to increased awareness, diagnosis and registration systems (2,3,6). Although breast CA is rare in young women, it is one of the leading causes of cancer-related deaths under the age of 40 (7,8). The survival rate in young breast cancer patients is lower than in older patients (4.9).
While the 5-year survival rate in breast cancer patients before the age of 40 is 82%, this rate is 89% in breast cancer patients aged 40 and over. stop (4). Although it is controversial, although young women receive more intensive treatment, young age is a risk factor for disease recurrence and death when cumulative data are evaluated (10-12).
Although younger women receive more intensive treatment, the lack of effective screening programs causes delays in diagnosis. Consequently, younger patients present with larger tumor masses and positive lymph nodes (13). However, differences in survival rates are mostly due to differences in the biological types of breast cancer. Compared to premenopausal and postmenopausal patients, breast CA subtypes that are more aggressive, have negative prognostic features, and are less responsive to conventional treatments develop in young women (14-16). Specifically, tumors in young women, high grade, hormone receptor negative, and high proliferation fraction indicate more lymphovascular invasion.
In a Korean study, 1444 women under the age of 35 and 8441 women between the ages of 35-50 were examined and the age at diagnosis was evaluated. Relevant clinocopathological differences were detected. Women under the age of 35 have larger tumors and more lymph nodes. Also young group a 32.4% ER positive, 30.6% ER negative, 37% unknown, in the older group, 36.6% ER positive, 27.8% ER negative, 35.5% ER unknown group. In addition, in the young group, 29.9% are PR positive, 31.9% are PR negative, and 38.2% are the unknown group. In the elderly group, 36.6% were PR positive, 27.6% were PR negative, and 35.8% were found to have unknown receptor status.
When ERBB2 status obtained by immunohistochemical scoring was evaluated, 263 women under the age of 35 and 35.8% in the elderly group No significant difference was found among the 1947 women included in the study (15). Recent studies have shown that breast cancers developing in young women have different biological characteristics and irregular oncogenic pathways such as Src and E2F, which may change the prognosis (17). Additionally, a growing body of evidence suggests that biological subtypes of breast cancer show racial differences. In large series studies examining age, race, and breast cancer subtypes, basal-like breast cancer subtype (ER (-), PR (-), ERBB2 (-), cytokeratin 5/6 (+), and/or ERBB1 (+)) was found to be premenopausal black. shows that it is more common in women (39%) than in postmenopausal black women (14%) and than in non-black women of any age group (16%) (18). In addition, it is reported that the good prognosis luminal A (ER (+) and/or PR (+), ERBB2 (-)) subtype is less common in premenopausal black women (36%, 59%, 54% respectively).
The risk of death due to breast cancer is high, and despite high-dose treatment, young patients face some age-specific problems. These problems, such as endangering their social lives during treatment, problems with fertilization, and attractiveness, are issues specific to this age group. Young women want to have children after treatment. These patients have increased genetic risk factors (19-22).
Risk Factors
Except for female gender, increasing age is the strongest risk factor for the development of breast cancer. As a result, young women have a lower risk than women in the premenopausal age group. The average risk of developing breast cancer in the twenties is 1/1800, in the thirties it is 1/230, in the forties it is 1/70 (4)
Family history, especially in young first-degree relatives who have developed breast cancer. Otherwise, it is the primary risk factor. Although 15-10% of breast cancers are due to BRCA 1 and BRCA 2 germ cell mutations on chromosomes 17 and 13, 15-20% of breast cancers were found to be related to gene pleomorphism and environmental factors (17). Considering age alone, younger female patients diagnosed with breast cancer are more likely to be BRCA mutation carriers. BRCA 1 or BRCA2 mutation was detected in 9% of patients under the age of 40 who underwent surgery for early breast cancer. Other risk factors, such as familial or personal ovarian cancer, bilateral breast cancer, or being of Ashkenazi Jewish ancestry, also create this risk. Unknown variants of BRCA1 and BRCA 2 also vary by race (23). Necessary counseling and testing regarding BRCA1 and BRCA 2 is recommended for young women diagnosed with breast cancer, especially in patients with a family history of breast and ovarian cancer.
In some rare genetic diseases, the susceptibility of young women to the development of breast cancer increases. . These are Cawden disease (PTEN gene mutation on chromosome 10, young age, hamartomas, breast and thyroid carcinoma), Li-fraumenia (TP53 mutation on chromosome 17, soft tissue bone sarcomas, brain tumor, adrenal tumor, breast cancer) (24), The risk of developing breast cancer is increased in case of exposure to ionizing radiation during childhood and adolescence (radiation exposure due to pediatric Hodgkin's disease) (25).
Despite existing prejudices, it has been observed that the development of breast cancer is spontaneous in young female patients. It has not been clearly associated with environmental and familial cancer syndromes. Hormonal and environmental factors for the development of breast cancer have not been clearly clarified in younger patients, unlike in older female patients. While breastfeeding has a preventive effect on the development of breast cancer in all age groups, pregnancy has two effects, such as the risk of developing breast cancer.
Large epidemiological studies show that while the risk of breast cancer increases in the 3-15 years after birth, this risk decreases in the following years (18, 31-34). Advanced maternal age at first birth temporarily increases the risk of breast cancer. After all, pregnancy is postmenopausal. While it is protective against breast cancer, advanced maternal age causes an increased risk in premenopausal pregnancies. The biological mechanism for this situation is not clearly clarified. In addition, unlike older female patients, weight gain and high BMI have a protective effect against the development of breast cancer at young ages (35-37).
Breast diagnostic procedures in young women
Most of the lesions that develop in young premenopausal women are benign. Mammography provides limited data in young women due to high tissue density (33-35). In this patient group, USG and MRI provide more information. Breast cancer may be larger in younger patients. The risk of multicentric or bilateral occurrence is not clearly known in the absence of hereditary predisposing factors. There is no evidence to show the effect of multifocality of the disease on survival (36-41).
Many clinical studies have divided patients into menopausal status, or age groups under and over 50 years of age. There are no published clinical studies on the treatment in young women. Publications publish relevant treatment in premenopausal women, which reflects the age group in their 40s.
Local treatment in young patients
Due to inadequate imaging techniques, large and large breast cancer patients are diagnosed with breast cancer. It appears locally and in advanced stages. Although data on these patients are limited, younger patients benefit more from preoperative systemic therapy than older patients. Although they benefit from radiotherapy to the tumor bed, young age is a risk factor for local recurrence in both invasive and non-invasive disease (42-47).
Evidence that mastectomy increases survival when mastectomy and breast-conserving surgery are compared in younger patients. not detected. In a population-based study conducted in Denmark, 9285 premenopausal breast cancer patients were examined, and while local recurrence after BCS was found to be 15.4% in 719 women under the age of 35, this rate was found to be 3% between the ages of 45 and 49. There was no difference in the risk of death between the two age groups (48), only age was a significant difference in terms of BCS. It does not create a trend. However, an increasing number of female patients prefer bilateral prophylactic mastectomy, not just mastectomy (49). Although there is no clear reason for this approach, there is no evidence that such an aggressive surgical intervention positively affects the results. For some young female patients, local treatment options are influenced by whether there is a known genetic risk for developing new primary cancers. Therefore, genetic tests should be performed and genetic counseling should be provided in terms of genetic mutation carriers, which may have an impact on local treatment decisions. Bilateral prophylactic mastectomy and oophorectomy are increasingly accepted in young patients with known BRCA 1 BRCA2 mutation carriers (50,51).
Currently, there is no data on the effect of radiotherapy and modern systemic treatment on cardiac functions in young women. Other effects of radiation therapy should be taken into consideration in patients with long life expectancy (52). Surgical margins are an important issue to consider in young women who undergo breast-conserving surgery. In a study conducted in 37 axilla-negative BCS patients younger than 35 years of age, local recurrence was found to be 50% in patients with positive surgical margins and 20.8% in patients with negative margins (45). In recent publications, local recurrence-free survival in women aged 40 and under with invasive disease was found to be 84.4% in patients with negative surgical margins and 34.6% in patients with positive surgical margins. The local recurrence-free survival rate in women aged forty and above was found to be 94.7% for negative surgical margins and 92.6% for positive surgical margins (46). When these findings were adjusted for 10-year disease-free survival, 72% disease-free survival was found in the young female patient with negative surgical margins and 39.7% in the young female patient with positive surgical margins. No significant difference was found in terms of disease-free survival rate in older age surgical margin-positive and negative female patients.
Systemic treatment
Adjuvant treatment recommendations depend on the characteristics of the tumor and the patient. In treatment, regardless of age, tumor subtypes and factors such as grade, proliferation rate, presence of estrogen and progesterone receptors and ERBB2 expression are evaluated.
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