Detailed Study Notes for BIOH12012 Week 11 - Female Reproductive Anatomy & Pathophysiology

Acknowledgement of Country

  • CQUniversity acknowledges Traditional Owners and Custodians and pays respect to the Elders of all First Nations peoples of Australia.

  • Presented by Dr Debra Carlson.

Breast Cancer

  • Second most commonly diagnosed cancer in Australia in 2020.

  • Reference: Cancer Australia, estimated cancer incidence in Australia, 2024.

Breast Anatomy

  • Mammary Glands:

    • Develop and differentiate after puberty.

  • Hormonal Control:

    • Hormones control the differentiation of mammary gland epithelium.

    • Influence the rate of stem cell division.

    • May act as accelerators or initiators of changes.

    • May influence the susceptibility of breast epithelium to environmental carcinogens.

  • Cell Proliferation:

    • Occurs during the luteal phase in the terminal ductal lobular units (TDLUs).

    • TDLU:

    • Consists of 10-100 acini that drain into the terminal duct.

    • Site of origin for:

      • Ductal carcinoma in situ (DCIS)

      • Lobular carcinoma in situ (LCIS)

      • Fibroadenoma

      • Fibrocystic disease (e.g., cysts)

    • Most invasive cancers arise from the TDLU.

Breast Cancer Overview

  • Definition: A neoplasm originating within breast tissue; affects the cells of breast tissue.

  • Malignant tumour locations:

    • Upper outer quadrant of the breast ≈ 50%.

    • Central portion of the breast; next most common location.

  • Cell Origin:

    • Majority arise from cells of the ductal epithelium.

  • Abnormal Changes:

    • Ductal Carcinoma In Situ (DCIS):

    • Usually confined to a single ductal system.

    • Lobular Carcinoma In Situ (LCIS):

    • Cells cluster non-cohesively in ducts and lobules.

Ductal Carcinoma In Situ (DCIS) and Lobular Carcinoma In Situ (LCIS)

  • DCIS:

    • Abnormal cells present in ducts.

  • LCIS:

    • Abnormal cells present in lobules.

Advanced and Metastatic Breast Cancer

  • Local Advanced Breast Cancer:

    • Invasion of skin, chest wall, nearby lymph nodes.

    • Obstruction of lymph nodes leading to lymphoedema.

  • Metastatic Breast Cancer:

    • Spread to distant tissues via bloodstream and lymphatic system.

    • Most common locations: bone, liver, lung, and brain.

Breast Cancer Pathophysiology

  • Triple-Negative Breast Cancers:

    • Do not respond to estrogen, progesterone, and HER2.

  • BRCA1 and BRCA2 genes:

    • Tumour-suppressor genes with a 50% chance of inheriting mutations.

  • DNA Modification:

    • Replicative immortality characterized by no senescence and gene mutations.

    • Suppression of apoptosis.

  • Chromosomal Features:

    • Estrogen receptor (ER) / Progesterone receptor (PR).

    • HER2 gene amplification or protein overexpression.

    • Tumour protein 53 (TP53) mutation.

Endometriosis

  • Definition: A condition where endometrial tissue is located outside of the uterine cavity.

  • Mechanism:

    • Retrograde menstrual flow: Migration of endometrial tissue into the peritoneal cavity during menstruation.

Stages of Endometriosis

  • Stage 1: Minimal invasion of endometrial tissue.

  • Stage 2: Deeper implantation of endometrial tissue.

  • Stage 3:

    • Moderate disease with many deep implants, endometriomas on one or both ovaries, and some adhesions.

  • Stage 4: Severe disease with many deep implants, large endometriomas on one/both ovaries, deep adhesions to posterior uterus and rectum.

Polycystic Ovary Syndrome (PCOS)

  • Overview:

    • Excessive androgen production due to inappropriate gonadotrophin secretion.

    • Prevents ovulation leading to enlargement and cyst formation in the ovaries.

    • Linked to metabolic disorders including obesity and insulin resistance.

  • Diagnostic Criteria: Two or three of the following:

    • Menstrual irregularity (anovulatory cycles or oligomenorrhoea).

    • Clinical hyperandrogenism (manifested as acne, hirsutism, male-pattern baldness, or biochemical evidence of elevated blood androgens).

    • Ultrasonic evidence of polycystic ovaries (12 or more enlarged follicles in each ovary with 2-9 mm in diameter or > 10 mL in volume).

Insulin Resistance in PCOS

  • High levels of insulin can lead to hormonal balance alterations, affecting LH, FSH, and androgen levels, contributing to anovulation.

Leiomyoma

  • Definition:

    • Leiomyomas are benign uterine tumors, often referred to as uterine fibroids.

  • Origin: Originate during reproductive years.

  • Types:

    • Intramural: Contained within the uterine wall.

    • Submucosal: Intrude into the uterine cavity.

    • Pedunculated: External to the uterine wall but tethered.

    • Subserosal: Located near the outer layer (serosa) of the uterus.

Symptoms of Leiomyoma

  • Symptoms vary depending on size and location:

    • Small tumors are often asymptomatic.

    • Heavy menstrual bleeding leading to iron-deficiency anemia.

    • Pelvic pressure due to compression (primarily in subserosal tumors).

    • Pain.

Female Reproductive Cancers

  • Upper and Lower Reproductive Tract Cancers:

    • Uterine Cancer: Cancer of the endometrium.

    • Ovarian Cancer: Cancer of the ovary.

    • Cervical Cancer: Cancer of the cervix.

    • Vaginal Cancer: Cancer of the vagina.

    • Vulvar Cancer: Cancer of the vulva.

Symptoms and Management of Female Reproductive Cancers

  • Common Symptoms:

    • Often vague and nonspecific: abnormal vaginal bleeding, abdominal pain, weight loss, bloating, constipation.

    • Specific symptoms: Malodorous vaginal discharge, postcoital bleeding, dysuria, dyspareunia, perivulvar pruritus.

  • Management Options:

    • Hysterectomy for symptomatic management.

    • Balance estrogen/progesterone levels.

    • Hormone Replacement Therapy (HRT).

    • Cytoreductive surgery, oophorectomy, cone biopsy, trachelectomy, vaginal hysterectomy, and vulvectomy as indicated.

Uterine Cancer

  • Prevalence: In 2018, uterine cancer was the 5th most commonly diagnosed cancer in females in Australia.

  • Risks:

    • Atypical endometrial hyperplasia: 28% of women with it develop endometrial cancer, driven by hormonal factors (excess estrogen).

Ovarian Cancer

  • Overview:

    • Often asymptomatic; about 75% of cases are diagnosed at an advanced stage.

  • Aetiology: Generally unknown, about 10% inherited (BRCA1, BRCA2, TP53 mutations).

  • Risk Factors: Increased ovulatory trauma, postmenopausal hormone therapy, protective effects from pregnancy and contraceptive use.

Clinical Manifestations of Ovarian Cancer

  • Often asymptomatic in early stages; nonspecific symptoms include abdominal bloating, appetite loss, unexplained weight changes, and fatigue.

  • Advanced stages may show symptoms of abdominal distention, pressure, or pain.

Ovarian Cancer Pathophysiology

  • Classification: Based on tissue of origin:

    • Epithelial Tumours: Serous adenocarcinoma, 70-90% of ovarian malignancies.

    • Germ Cell Tumour: Resembling embryonic tissue, ≈ 25% of ovarian tumours.

    • Sex Cord Tumour: ≈ 10% of ovarian tumours arising from connective tissue.

Metastatic Pattern of Ovarian Cancers

  • Malignant Progression:

    • Local shedding into peritoneal cavity, intra-abdominal spread, local invasion of bowel and bladder.

    • Staged I to IV:

    • Stage I: Limited to one or both ovaries.

    • Stage II: Extends into pelvis.

    • Stage III: Metastases outside the pelvis.

    • Stage IV: Distant metastases.

Summary Notes on PCOS

  • Hyperandrogenism Manifestations: Acne, hirsutism, male-pattern hair loss, elevated serum androgens.

  • Polycystic Ovaries on Ultrasound: Associated with obesity and insulin resistance.

  • Menstrual Dysfunction: Oligomenorrhoea or amenorrhea.

  • Treatment Options: Include weight loss, oral contraceptives, spironolactone.