Genetic predisposition in breast cancer

 

Genetic predisposition; Approximately 10% of breast cancers are inherited and associated with a family history, although this varies frequently by ethnicity and across countries in the context of early-onset, bilateral and/or TNBC. Individuals with a first-degree relative who had breast cancer have an elevated relative risk (RR) of 3 of early-onset breast cancer (before 35 years of age).

However, a family history of breast cancer is associated with an ‘erratic’ individual risk of breast cancer composed of different variables, including the size of the family and environmental factors. To determine the family’s risk, models such as the family history score have been developed.

Mutations in two high-penetrance tumour suppressor genes, BRCA1 and BRCA2, whose proteins are involved in DNA repair through homologous repair, show an autosomal-dominant inheritance pattern (loss of function>missense). BRCA1 and BRCA2 mutations are associated with an average cumulative risk of developing breast cancer by the age of 80 years of 72% and 69%, respectively; the relative risk of breast cancer in men harbouring BRCA2 mutations is 6%.

More than 2,000 BRCA gene alterations have been described (mutations and large rearrangements), but only few have been found repeatedly in unrelated families, for example, founder mutations in Ashkenazi Jewish families (BRCA1 185delAG or BRCA2 6174delT) or Icelandic families (BRCA2 999del5).

The prevalence of BRCA1 and BRCA2 mutations varies between ethnic groups, being lower in the Asian group (0.5%) and higher in the Ashkenazi group (10.2%) in a US nationwide study. Germline BRCA testing will now be performed as a companion diagnostic in patients with metastatic breast cancer given the availability of poly(ADPribose) polymerase (PARP) inhibitors, which prolong progression-free survival (PFS) and improve quality of life, as a targeted therapy for BRCA mutation carriers in HER2-negative metastatic breast cancer.

Several syndromes related to germline mutations of genes involved in DNA repair and maintaining genomic integrity have been shown to be linked to, to a lesser degree, the inherited breast cancer risk. Next-generation sequencing has enabled panels of genes to be screened — beyond BRCA1 and BRCA2 — to determine the inherited breast cancer risk, and include ATM, CHEK2, PALB2, PTEN, STK11 and TP53.

Trichomoniasis clinical manifestations

Women who are symptomatic from trichomoniasis complain of vaginal discharge, pruritus, and irritation. Signs of infection include vaginal discharge (42%), odor (50%), and edema or erythema (22 to 37%). The discharge is classically described as frothy, but it is actually frothy in only about 10% of patients. The color of the discharge may vary. Colpitis macularis (strawberry cervix) is a specific clinical sign for this infection but is detected with reliability only by colposcopy and rarely during routine examination.

Other complaints may include dysuria and lower abdominal pain; the etiology of the latter is unclear. The urethra is also infected in the majority of women. Nearly half of all women with trichomoniasis vaginalis are asymptomatic. Therefore, if these women are not screened, the diagnosis will be missed.

The extent of the inflammatory response to the parasite may determine the severity of the symptoms. Factors that influence the host inflammatory response are not well understood but may include hormonal levels, the coexisting vaginal flora, and the strain and relative concentration of the organisms present in the vagina.

Breast cancer signs

 Chris McKeen/Stuff

Radio personality Sarah Gandy is distributing new stickers that educate females about the nine symptoms of breast cancer.

The day before New Zealand went into level 4 lockdown, Sarah Gandy had her final cancer treatment.

The former The Hits breakfast radio host found a lump in her breast in 2018, aged just 36.

Chris McKeen/Stuff

Sarah Gandy first learned of her breast cancer at 36.

It turned out to be two “huge” tumours, one of which measured 8cm by 7cm, requiring her to undergo a full mastectomy and months of chemotherapy and radiation.

Her experience has prompted her to join forces with the Breast Cancer Foundation to launch the ‘Change & Check’ campaign on October 1, marking the start of Breast Cancer Awareness Month.

READ MORE:* Radio host Sarah Gandy diagnosed with breast cancer after losing job at The Hits* Mum-of-three leads campaign highlighting growing rate of breast cancer in young women* Young Hamilton mum bares all for breast cancer

Of the nine major signs of breast cancer, Gandy said she knew of two when she was diagnosed.

Speaking to Stuff from her West Auckland home, Gandy she had been struggling with panic attacks for a few months when she found the lump in late 2018.

Trichomoniasis treatment

Trichomoniasis treatment, until recently, metronidazole was the only efficacious antibiotic available in the United States for the treatment of trichomoniasis. The recommended dose is 2 g orally in a single dose, and the reported cure rate is 97%. Sexual partners should also be treated. Metronidazole intravaginal gel has limited efficacy and should not be used.

Although there continues to be some controversy about the safety of metronidazole in pregnancy, there has never been a documented case of fetal malformation attributed to its use, even when it is used in the first trimester. Recently, controversy has also developed concerning the treatment of trichomoniasis in pregnancy and its relationship to preterm birth.

Trichomoniasis treatment on pregnant women. Two studies have recently been published which suggest that treatment of trichomoniasis in pregnancy may actually increase the risk of preterm birth rather than decrease the risk as predicted. However, there are limitations to both of these studies. One of the studies used much higher doses of metronidazole than are recommended. In addition, the study was stopped prematurely because of the trend toward preterm birth that was seen, and so the number of women enrolled fell short of the number needed for a definitive analysis. The second study was a subanalysis of a study designed to answer questions relating to STD (sexual transmition diseases) and HIV risk, therefore, it was not designed primarily to answer questions regarding the risks of preterm birth associated with treatment of trichomoniasis in pregnancy.

Since the publication of these papers, the Centers for Disease Control and Prevention has not revised recommendations for treatment during pregnancy. Pregnant women may be treated with the 2-g single dose of metronidazole. Occasionally patients are allergic to metronidazole. Since there is no effective alternative, desensitization is the only option. Another therapeutic dilemma involves metronidazole resistance in Trichomoniasis vaginalis. The mechanism of development of anaerobic resistance to metronidazole also is controlled by hydrogenosomes, in that metronidazole competes for H
as an electron acceptor. In metronidazole-resistant trichomoniasis vaginalis, the expression levels of the hydrogenosomal enzymes pyruvateferredoxin oxidoreductase, ferridoxin, malic enzyme, and hydrogenase are reduced dramatically, which probably eliminates the ability of the parasite to activate metronidazole.

Early warning signs for breast cancer

 Early warning signs for breast cancer

Breast cancer affects millions of women across the globe every year. According to the World Health Organization, breast cancer is the most frequent cancer among women, affecting 2.1 million women each year. As daunting as that may seem, the WHO also notes that early diagnosis can greatly reduce a woman’s risk of dying from breast cancer.

Women can be proactive in the fight against breast cancer by learning to identify early warning signs of the disease. The nonprofit breast cancer advocacy organization Susan G. Komen® notes that the warning signs for breast cancer are not the same for all women, but the most common signs include a change in the look or feel of the breast or a change in the look or feel of the nipple. A discharge from the nipple is another common warning sign of breast cancer.

Physical changes in the breast can vary, but Susan G. Komen® advises women who notice these changes to bring them to the attention of their physicians immediately:

♦ Lump, hard knot or thickening inside of the breast or underarm area

♦ Change in the size or shape of the breast

♦ Swelling, warmth, redness or darkening of the breast

♦ Dimpling or puckering of the skin

Breast cancer in men

Breast cancer in men, The male breast is a rudimentary organ that is limited to ducts in the retro-aerolar area, expressing oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR). Benign and malignant lesions presenting as retro-aerolar lumps can occur, although male breast cancer is rare: less than 1% of all breast cancers occur in men and less than 0.5% of deaths in men can be attributed to breast cancer.

The lifetime risk for breast cancer in men is 1 in 833 compared with 1 in 10 for a woman. Of affected men, 20% have a first- degree family history of cancer; 4–14% of cases in males are attributed to germline BRCA2 mutations and there is a 60–76% chance of a BRCA2 mutation in families with at least one affected male. Klinefelter syndrome engenders a relative risk of 30–50 for male breast cancer (owing to elevated circulating oestrogens); 5% of men with breast cancers have this syndrome.

Other risk factors for breast cancer development in men include elevated oestrogens (imbalance of oestrogen and testosterone), liver cirrhosis, prostate cancer, age, obesity and smoking. In individuals who undergo male-to-female gender reassignment, hormonal stimulation may promote breast cancer development.

Clinically, men with breast cancer present at older age (60–70 years) and with higher stage than women with breast cancer. Invasive ductal carcinoma is the most frequent subtype, whereas invasive lobular carcinoma is extremely rare compared with female breast cancer; papillary carcinoma is the second most frequent histological type.

In terms of the intrinsic subtypes, >90% of male breast cancers are luminal A or luminal B; human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer are extremely rare in men. AR is often overexpressed in male breast cancer. Expression pathways of luminal genes are also predominant; activation of fibroblast growth factor receptor 2 (FGFR2) and phosphatidylinositol 3-kinase (PI3KCA) pathways are potential therapeutic targets to be explored in the future. Prognosis is similar to stage-matched women with breast cancer, although overall survival is worse because male patients with breast cancer are often older, have more comorbidities and have lower life expectancy. Treatments are largely extrapolated from female breast cancer, due to a paucity of available data.

As the vast majority of breast cancers in men are luminal cancers, the most important therapy is endocrine therapy. In the adjuvant setting, tamoxifen (which binds to and inhibits the ER) is the standard of care and aromatase inhibitors should not be used alone (as these are associated with worse survival). In cases of absolute contra-indication for tamoxifen use, a combination of an aromatase inhibitor and a luteinizing hormone-releasing hormone agonist can be considered, although this approach is associated with higher toxicity. Recommendations for adjuvant chemotherapy and radiation therapy are similar to those in women with luminal early breast cancer, as are recommendations for management of advanced breast cancer.

Vitamins for kids

Vitamins are a powerful weapon that is always used by almost all parents in order to maintain and increase the child's immune system. Especially if the weather is not friendly, which makes children vulnerable to contracting diseases. The supplements or vitamins chosen also have various forms, ranging from capsules, syrups, or tablets with a sweet taste that are very popular with children. 

 Immunomodulators, how this supplement is often called by health experts, works by improving the function of immunity in the body by stimulating the work of this immunity. The stimulation is given from the ingredients contained in the supplement. 

The dangers of giving supplements to children arbitrarily

 Unlike ordinary vitamins, immunomodulators are not recommended for long-term consumption. The impact of this children's supplement will respond to excessive body immunity, which can cause allergies and hypersensitivity in children. This is why parents are advised to only provide supplements if the child has immune problems, such as long-term coughing, frequent colds and flu, so that they are prone to infection. This does not mean that supplements should not be given to healthy children. It's okay, as long as it's not for a long or prolonged period.

Also read: Why does your little one need to take a nap?

Instead of giving vitamins or supplements for a long time, a nutritionist who is also a herbalist, Jennifer Crain said, providing nutritious food and meeting children's daily nutritional intake is much better and recommended. We recommend that you avoid giving supplements when the child is in good health.

Also in a study published in the journal Pediatric and Adolescent Medicine wrote that the majority of children and adolescents in the United States who take supplements every day actually do not need this intake. On the other hand, children who need supplement intake cannot get it for various reasons, one of which is the low economy.