Breast, Ovarian and Cervical Cancer: The Diagnostic Workup

The diagnostic workup for breast, ovarian and cervical cancer follows one discipline: examine, image, then take tissue from the safest site that will answer the question, and stage before treating. Dr. Niti Raizada, Principal Director Medical Oncology, Fortis Hospital, Bannerghatta Road, Bengaluru, India, worked through three cases that show where each step can go wrong.

Breast, cervical and ovarian cancers still kill women who could have been cured, and they matter disproportionately in Africa. Dr. Raizada noted that breast cancer and cervical cancer are the two leading causes of cancer death there across both sexes, even though both are among the most curable cancers when found on time. The broader picture, including screening schedules and HPV vaccination, is in the complete guide to diagnosing common cancers and blood disorders.

Breast cancer in a young woman: why age is not reassurance

Age under 40 does not rule out breast cancer. A hard, irregular lump, an enlarged armpit node or a strong family history of premenopausal breast or ovarian cancer calls for triple assessment at any age.

The presentation

A married woman in her mid-thirties, who had been seeing fertility specialists because she had not been able to conceive, came to Dr. Raizada with a painless lump in the right breast that had been growing for two months. Her periods were regular.

A detailed history changed the picture. Her mother had breast cancer and her aunt had ovarian cancer, and both were premenopausal at diagnosis, at 45 and 47 respectively.

On examination, the mass in the upper outer quadrant of the right breast measured about 4 by 3 cm and was hard and irregular. There was a 1.5 cm lymph node in the right armpit.

Why the red flag was easy to dismiss

In a woman in her twenties or thirties, cancer is rarely the first diagnosis that comes to mind. Dr. Raizada's point was that this case was not ambiguous once the facts were assembled: a hard, irregular mass, an enlarged axillary node and two close relatives with premenopausal breast and ovarian cancer. Any one of these should prompt investigation; together they demand it.

Triple assessment: examination, imaging, biopsy

Every breast lump is assessed in three steps, known as triple assessment.

1. Clinical examination, recording the characteristics of the lump.
2. Imaging. In women under 40, the first test is a breast ultrasound. From 40, a mammogram is done. Where suspicion is high, a mammogram may be done in a younger woman as well.
3. Biopsy, if anything is suspicious. Dr. Raizada insists on a core needle biopsy, which removes a cylinder of tissue, rather than fine needle aspiration, which samples only cells.

Alongside this, baseline blood work was done and a beta-hCG test ruled out pregnancy, because several investigations cannot be performed in a pregnant woman.

The ultrasound showed a BI-RADS 4 lesion, meaning a suspicious finding that needs a biopsy. Given the high suspicion, a mammogram was also done; it showed a spiculated mass (one with irregular, spiky margins) with microcalcifications. The core biopsy confirmed invasive ductal carcinoma, grade 2.

Receptor status decides the treatment plan

Once cancer is confirmed, the subtype has to be established. The biopsy was tested for the oestrogen receptor, the progesterone receptor and HER2. All three were negative, which defines triple-negative breast cancer.

Dr. Raizada described triple-negative breast cancer as a distinctive variant in young women and the most aggressive type of breast cancer. It behaves as a systemic disease and needs urgent, aggressive management.

Why surgery was not the first step

Contrary to what most people assume, the first treatment was not surgery. The patient first had a PET-CT scan, which Dr. Raizada uses in place of separate CT scans of the chest, abdomen and pelvis plus a bone scan. PET-CT is easy to access in Indian cities, works out cost-effective, and is reported within hours; some newer scans do not even require fasting. The main precaution is a kidney function test so that contrast can be given safely. The scan showed no metastatic spread.

She then received neoadjuvant chemotherapy (chemotherapy before surgery), to be followed by surgery. For how surgeons sequence breast cancer treatment by stage and subtype, see Dr. Rajesh Kumar Jain's article on breast cancer treatment protocols; costs for surgery are on the breast cancer surgery cost page.

Fertility preservation is part of the plan

Because the patient was young and her cancer was curable, a fertility discussion was the norm, particularly since conceiving had been her goal. Dr. Raizada's options:

• Married women: embryo cryopreservation.
• Unmarried women: oocyte harvesting and freezing, or ovarian tissue cryopreservation.

Genetic testing and what a positive result means

With such a strong family history, she was offered genetic testing, a blood test. It found a mutation that places her at higher risk of familial cancer. Dr. Raizada explained what that means: the cancer can be bilateral, and carriers face a higher risk of cancers elsewhere, such as the ovaries or pancreas, and, in men carrying the same mutation, prostate cancer.

Ovarian cancer diagnosis: the biopsy you must never take

A suspected ovarian cancer is investigated with a transvaginal ultrasound, CA 125 and a CT scan. Where there is peritoneal disease, tissue comes from a guided biopsy of the omentum or peritoneum, never from a needle in the ovarian mass.

The presentation

A postmenopausal woman in her sixties, with three children and well-controlled hypertension, saw a gynaecologist with one month of abdominal distension. She felt full after eating very little (early satiety), had a dragging, heavy pelvic pain when she walked, and became breathless when lying down. She had no family history of cancer.

Transvaginal ultrasound and CA 125

A transvaginal ultrasound and a CA 125 blood test were the first investigations. The scan showed a 10 cm left adnexal mass, solid and cystic, with internal septations and papillary projections, and moderate ascites that could be felt clinically. CA 125 was raised.

Dr. Raizada's checklist of features that point to a malignant ovarian mass:

• Usually a postmenopausal woman
• A rapidly growing mass, often larger than 8 cm, on one or both sides
• Irregular, solid or complex (solid and cystic) structure
• A thick, irregular wall
• Papillary projections, which are particularly characteristic of serous carcinoma
• Ascites
• Increased vascularity
• A raised CA 125

She also checks CEA, a second tumour marker, to rule out a Krukenberg tumour (a cancer that has spread to the ovary from the stomach or bowel).

Getting tissue safely

A CT scan confirmed the large left ovarian mass and showed large deposits on the peritoneum, including omental caking (the fatty apron of the abdomen thickened by tumour). The chest CT was normal.

Here Dr. Raizada was emphatic: if the only lesion is the ovarian mass, never put a needle into the ovary to biopsy it. Where there is peritoneal disease, a guided biopsy is taken from the omentum or peritoneum instead. In this patient, the omental biopsy showed high-grade serous carcinoma, which she noted is often the histology in these cases.

Ovarian cancer is known as a silent killer because symptoms are so mild that most women present late, as this patient did. Dr. Punyashree R M's article on early ovarian cancer symptoms covers the symptoms from a gynaecological oncology perspective.

Chemotherapy first, then cytoreductive surgery

The extent of peritoneal disease made upfront surgery difficult. Chemotherapy was started first, followed by cytoreductive surgery (CRS) to remove all visible tumour, combined with hyperthermic intraperitoneal chemotherapy (HIPEC), in which heated chemotherapy is circulated through the abdomen during the operation. Costs are on the CRS and HIPEC cost page.

Endometrial thickness after menopause

After menopause, Dr. Raizada treats an endometrial thickness of 5 mm or more as significant when there is vaginal bleeding. She flagged uterine (endometrial) cancer as an important emerging problem, and the key measurement is endometrial thickness on ultrasound in a postmenopausal woman.

• With postmenopausal vaginal bleeding: a thickness of 5 mm or more needs an endometrial biopsy.
• Without bleeding: she treats a thickness of up to 8 mm as acceptable.

Guidelines set no single cut-off for women without bleeding, and tamoxifen itself thickens the endometrium, so in these groups thickness is interpreted alongside symptoms and risk. Dr. Punyashree R M's article on endometrial thickness and endometrial cancer covers the condition in more depth.

Cervical cancer diagnosis: from punch biopsy to chemoradiation

Cervical cancer is diagnosed by a speculum examination and a punch biopsy of the visible growth, then staged with MRI of the pelvis and imaging of the chest and abdomen. Stage IIB disease is treated with concurrent chemoradiation.

The presentation

A postmenopausal woman in her fifties had three months of irregular vaginal bleeding, heavy whenever it occurred, with a foul-smelling discharge and a month of pelvic pain. She had had full-term deliveries, the last about 20 years earlier, no history of oral contraceptive use, and had never had regular cervical screening.

Examination and biopsy in one visit

Abdominal examination was normal. A speculum examination showed a friable growth on the cervix that bled on touch, enough to soak several gauze swabs. The cervix was hard and indurated, and so was the parametrium (the tissue beside the cervix), which is assessed by rectal examination. A punch biopsy taken during the examination showed squamous cell carcinoma.

Her haemoglobin was low from the bleeding, but her other tests were normal. Kidney function was normal and there was no hydronephrosis (a swollen kidney from a blocked ureter, a sign of advanced spread).

Staging the disease

An MRI showed the tumour extending from the cervix into the upper vagina, with parametrial involvement but no spread to the bladder or rectum. That is stage IIB cervical cancer.

On imaging choice, a question raised in the masterclass Live Discussion, Dr. Raizada considers MRI of the pelvis very good, because pelvic structures are seen best on MRI. The upper abdomen and chest still have to be assessed. Her recommendation is either an MRI of the abdomen and pelvis with contrast plus a contrast CT of the chest, or a contrast CT of the chest, abdomen and pelvis. The chest is always better seen on CT; the pelvis is better seen on MRI. In practice in India, the staging scan is often a PET scan, which shows whether the lymph nodes or distant organs are involved, while MRI remains the better test for the parametrium, bladder and rectum.

Checking fitness for chemotherapy

Before treatment, Dr. Raizada confirms that chemotherapy will be safe. The pre-chemotherapy workup includes a GFR study, a functional kidney scan, and audiometry to check hearing. The sequence is therefore biopsy, staging scan, pre-chemotherapy workup, then treatment.

Concurrent chemoradiation

The standard treatment for stage IIB disease is concurrent chemoradiation: five weeks of external radiotherapy with weekly chemotherapy, followed by intracavitary brachytherapy, in which a radiation source is placed inside the vagina and cervix. Because the parametrium is involved, it is included in the radiation field. In certain locally advanced cases like this one, Dr. Raizada adds immunotherapy. Regulatory approvals for immunotherapy with chemoradiation cover higher-stage disease (FIGO 2014 stage III to IVA), so its use at stage IIB is a specialist decision. Patients are told in advance that radiation can cause temporary side effects.

The cure rate is very good, and identifying the disease on time is the key. Costs are on the radiotherapy cost page and the immunotherapy cost page.

Risk factors

Dr. Raizada associated cervical cancer with poor personal hygiene, multiple sexual partners and, above all, human papillomavirus (HPV). Persistent infection with high-risk HPV is the cause of almost all cervical cancers; other factors act largely by making infection or its persistence more likely. That is why cervical cancer is preventable, through vaccination and screening. Dr. Punyashree R M's article on cervical cancer elimination covers the screening and vaccination programme from a gynaecological oncology perspective.

One diagnostic workup for breast, ovarian and cervical cancer

Each case turned on taking the right tissue at the right moment. In the breast, that meant a core biopsy rather than a needle aspirate. In the ovary, it meant a biopsy of the omentum rather than the ovary. In the cervix, it meant a punch biopsy at the first examination. Each was then staged before a single treatment decision was made. The same discipline applies to lung, colon, liver and oral cancer. More on cancer care across specialties is on the oncology hub.